Broadly targeted human monoclonal antibodies against coronaviruses

Abstract

Monoclonal antibodies and antigen-binding fragments that specifically bind to coronavirus spike proteins, such as SARS-CoV-2, are disclosed. Use of these antibodies to inhibit coronavirus infection is also disclosed. Additionally, methods are disclosed for detecting coronaviruses in biological samples using the disclosed antibodies. A panel of human monoclonal antibodies (mAbs) that target multiple coronaviruses have been isolated. These mAbs inhibit coronavirus infection and can therefore be used as prophylactics to block coronavirus infection and as tools for the development of next-generation vaccines that provide more broad protection against coronaviruses.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This claims the benefit of U.S. Provisional Application No. 63 / 308,898, filed February 10, 2022, which is incorporated herein by reference in its entirety.

[0002] This relates to monoclonal antibodies and antigen-binding fragments that specifically bind to coronavirus spike proteins and their use to inhibit or detect coronavirus infection in a subject.

[0003] Electronic Sequence Listing Reference The contents of the Electronic Sequence Listing (4239-107907-02 ST26 SL.xml; size: 432,282 bytes; created February 4, 2023) are incorporated herein by reference in their entirety. [Background technology]

[0004] The novel coronavirus SARS-CoV-2 emerged in 2019, infecting 400 million people and causing over 5 million deaths worldwide. While effective vaccines and antibody therapeutics have been developed, their effectiveness is threatened by the emergence of variants of concern, including omicron variants, which are more resistant than previous variants to many of these tools. Furthermore, the possibility of additional coronavirus spillover from reservoir animals remains, and preparations must be made. Antibodies that bind to multiple coronaviruses remain needed. Summary of the Invention [Means for solving the problem]

[0005] We have isolated a panel of human monoclonal antibodies (mAbs) that target multiple coronaviruses. These mAbs inhibit coronavirus infection and can therefore be used as prophylactic agents to block coronavirus infection and as tools for the development of next-generation vaccines that provide more broad protection against coronaviruses.

[0006] Disclosed is an isolated monoclonal antibody or antigen-binding fragment that specifically binds to a coronavirus spike protein and neutralizes SARS-CoV-2 and at least one additional betacoronavirus or alphacoronavirus.

[0007] Disclosed are isolated monoclonal antibodies or antigen-binding fragments thereof that specifically bind to coronavirus spike proteins. These monoclonal antibodies or antigen-binding fragments are capable of neutralizing at least one coronavirus.

[0008] In some embodiments, the antigen or antigen-binding fragment comprises a heavy chain variable (V H ) region and the light chain variable region (V L ) and a) SEQ ID NOs: 17 and 21 (COV44-79), respectively; b) SEQ ID NOs: 9 and 13 (COV44-62), respectively; c) SEQ ID NOs: 1 and 5 (COV89-22), respectively; d) SEQ ID NOs: 25 and 29 (COV30-14), respectively; e) SEQ ID NOs: 33 and 37 (COV72-37), respectively; f) SEQ ID NOs: 49 and 53 (COV91-27), respectively; g) SEQ ID NOs: 41 and 45 (COV93-03), respectively; h) SEQ ID NOs: 57 and 61 (COV49-51), respectively; i) SEQ ID NOs: 65 and 69 (COV44-74), respectively; j) SEQ ID NOs: 73 and 77 (COV44-56), respectively; k) SEQ ID NOs: 81 and 85 (COV44-26), respectively; l) SEQ ID NOs: 89 and 93 (COV44-54), respectively; m) SEQ ID NOs: 97 and 101 (COV23-01), respectively; n) SEQ ID NOs: 105 and 109 (COV49-03), respectively; o) SEQ ID NOs: 113 and 117 (COV49-04), respectively; p) SEQ ID NOs: 121 and 125 (COV49-05), respectively; q) SEQ ID NOs: 129 and 133 (COV49-06), respectively; r) SEQ ID NOs: 137 and 141 (COV49-07), respectively; s) SEQ ID NOs: 145 and 149 (COV49-18), respectively; t) SEQ ID NOs: 153 and 157 (COV49-23), respectively; u) SEQ ID NOs: 161 and 165 (COV49-28), respectively; v) SEQ ID NOs: 169 and 173 (COV49-30), respectively; w) SEQ ID NOs: 177 and 181 (COV49-33), respectively; x) SEQ ID NOs: 185 and 189 (COV49-42), respectively; y) SEQ ID NOs: 193 and 197 (COV49-47), respectively; z) SEQ ID NOs: 201 and 205 (COV49-54), respectively; aa) SEQ ID NOs: 209 and 213 (COV57-01), respectively; bb) SEQ ID NOs: 217 and 221 (COV57-03), respectively; cc) SEQ ID NOs: 225 and 229 (COV57-04), respectively; dd) SEQ ID NOs: 233 and 237 (COV57-05), respectively; ee) SEQ ID NOs: 241 and 245 (COV57-13), respectively; ff) SEQ ID NOs: 249 and 253 (COV57-19), respectively; gg) SEQ ID NOs: 257 and 261 (COV57-34), respectively; hh) SEQ ID NOs: 265 and 269 (COV57-38), respectively; ii) SEQ ID NOs: 273 and 277 (COV57-45), respectively; jj) SEQ ID NOs: 281 and 285 (COV77-02), respectively; kk) SEQ ID NOs: 289 and 293 (COV77-04), respectively; ll) SEQ ID NOs: 297 and 301 (COV77-05), respectively; mm) SEQ ID NOs: 305 and 309 (COV77-09), respectively; nn) SEQ ID NOs: 313 and 317 (COV77-14), respectively; oo) SEQ ID NOs: 321 and 325 (COV77-35), respectively; pp) SEQ ID NOs: 329 and 333 (COV77-39), respectively; qq) SEQ ID NOs: 337 and 341 (COV77-42), respectively; rr) SEQ ID NOs: 345 and 349 (COV77-43), respectively; ss) SEQ ID NOs: 353 and 357 (COV77-46), respectively; tt) SEQ ID NOs: 361 and 365 (COV77-76), respectively; uu) SEQ ID NOs: 369 and 373 (COV93-04), respectively; vv) SEQ ID NOs: 377 and 381 (COV93-08), respectively; ww) SEQ ID NOs: 385 and 389 (COV93-17), respectively; xx) SEQ ID NOs: 393 and 397 (COV93-18), respectively; yy) SEQ ID NOs: 401 and 405 (COV93-23), respectively; zz) SEQ ID NOs: 409 and 413 (COV78-36), respectively; aaa) SEQ ID NOs: 417 and 421 (COV93-38), respectively; bbb) SEQ ID NOs: 425 and 429 (COV93-60), respectively; ccc) SEQ ID NOs: 433 and 437 (COV93-61), respectively; ddd) SEQ ID NOs: 441 and 445 (COV89-03), respectively; eee) SEQ ID NOs: 449 and 453 (COV89-28), respectively; fff) SEQ ID NOs: 457 and 461 (COV30-35), respectively; ggg) SEQ ID NOs: 465 and 469 (COV30-80), respectively; hhh) SEQ ID NOs: 473 and 477 (COV44-25), respectively; or iii) SEQ ID NOs: 481 and 485 (COV44-37), respectively V shown as one of H and V L V comprising heavy chain complementarity determining regions (HCDR) 1, HCDR2, and HCDR3, and light chain complementarity determining regions (LCDR) 1, LCDR2, and LCDR3 of H and V L Includes.

[0009] In some embodiments, nucleic acid molecules encoding these antibodies and antigen-binding fragments, vectors containing these nucleic acid molecules, and host cells containing these vectors are disclosed.

[0010] Pharmaceutical compositions comprising the antibodies, antigen-binding fragments, nucleic acid molecules, and vectors are also disclosed. In further embodiments, the use of these pharmaceutical compositions for inhibiting coronavirus infection in a subject is disclosed.

[0011] In yet other embodiments, the use of the disclosed antibodies and antigen-binding fragments for the detection of coronavirus in biological samples is disclosed.

[0012] The above and other features and advantages of the present invention will become more apparent from the following detailed description of several embodiments, which proceeds with reference to the accompanying drawings. [Brief explanation of the drawings]

[0013] [Figure 1]Broadly reactive antibodies target multiple human coronaviruses. Heatmap showing binding of broadly reactive mAbs to the spike proteins of various coronaviruses. Binding is shown for SARS-CoV-2 Wuhan Hu-1, SARS-CoV-1, MERS-CoV, HCoV-HKU1, HCoV-OC43 (betacoronaviruses); HCoV-NL63 and HCoV-229E (alphacoronaviruses), and H1 hemagglutinin (control). Malaria mAb L9 was included as a negative control for mAb binding experiments (Wang, LT et al. 2020). Area under the curve (AUC) values ​​for each antigen are shown after subtraction of the value for the negative control antigen, CD4. [Figure 2] The SARS-CoV-2 spike protein S2 subunit is a common target for broadly reactive antibodies. The heatmap shows binding values ​​to selected domains within the SARS-CoV-2 spike protein: the receptor-binding domain (RBD), the N-terminal domain (NTD), and the S2 subunit (n = 1 representative experiment). Area under the curve (AUC) values ​​are shown after subtraction of the value for the negative control antigen, CD4. [Figure 3] Broadly reactive mAbs target distinct epitopes within the SARS-CoV-2 S2 subunit. Surface plasmon resonance (SPR)-based analysis of binding to recombinant SARS-CoV-2 S2 subunit identified three distinct epitope bins for broadly reactive mAbs (numbering in inset). Dark gray boxes indicate competing antibody pairs, light gray boxes indicate non-competing antibody pairs, and hashed fill indicates self-competition. [Figure 4-1]Antibodies binding to the S2 fusion peptide, stem-helix region, and K814+ site. SPR-based peptide scanning analysis identified the S2 fusion peptide (FP), stem helix (SH), and the S2' cleavage site and site N-terminal to the fusion peptide region (K814+) as three distinct epitopes targeted by broadly reactive mAbs. Heat maps show binding to a panel of 15-mer peptides with a 12-amino acid overlay covering the entire S2 subunit for (A) the fusion peptide mAb and (B) the stem-helix mAb. Each column in the heat map represents a single peptide. Open triangles indicate the S1 / S2 cleavage site, and closed triangles indicate the S2' cleavage site. FP, fusion peptide; HR1, heptad repeat 1; C helix, central helix; CD, connector domain; SH, stem helix; HR2, heptad repeat 2. In Figure 4A, SEQ ID NO:491 is the amino acid sequence of peptide 42, SEQ ID NO:492 is the amino acid sequence of peptide 43, and SEQ ID NO:493 is the amino acid sequence of peptide 44. In Figure 4B, SEQ ID NO:494 is the amino acid sequence of peptide 153, SEQ ID NO:495 is the amino acid sequence of peptide 154, and SEQ ID NO:496 is the amino acid sequence of peptide 155. [Figure 4-2] Same as above. [Figure 5-1] Broadly reactive antibodies target highly conserved regions within the coronavirus spike protein. (A) Sequence conservation of the fusion peptide determined by alignment of spike protein sequences from 34 virus isolates representing diverse groups of coronaviruses across four genera. (B) Sequence conservation of the stem-helix region determined by alignment of spike protein sequences from 28 virus isolates representing each of the five betacoronavirus subgenera. Heatmap coloring indicates percent identity of amino acid residues. (C-F) Peptide sequences used in Figures 5A and 5B are provided as SEQ ID NOs: 499-562; see also Figures 5C-5F. [Figure 5-2] Same as above. [Figure 5-3] Same as above. [Figure 5-4] Same as above. [Figure 5-5] Same as above. [Figure 5-6] Same as above. [Figure 6] Broadly reactive antibodies neutralize multiple human coronaviruses and SARS-CoV-2 variants of concern. Neutralization of SARS-CoV-2 wild-type (WT) and variants of concern (pseudoviruses) by (A) fusion peptide mAbs COV44-62 and COV44-79 and (B) stem-helix mAbs COV30-14, COV72-37, and COV89-22. Dotted lines indicate 50% neutralization. Error bars indicate mean ± SD. [Figure 7] Broadly reactive antibodies inhibit SARS-CoV-2 spike-mediated fusion with target cells. In vitro fusion inhibition by (A) fusion peptide mAbs (COV44-62, COV44-79, COV91-27, COV77-04, COV77-39, and COV78-36) and (B) stem-helix-specific mAbs (COV30-14, COV72-37, and COV89-22) and K814+-specific mAbs (COV77-43 and COV93-18) in quantitative assays. Malaria mAb L9 and CoV-2 RBD-specific mAb CV503 were used as negative controls. [Figure 8] Broadly reactive antibodies limit SARS-CoV-2-mediated pathology in hamsters. Body weight change in SARS-CoV-2-exposed Syrian hamsters after prophylaxis with individual (A) fusion peptide and (B) stem-helix mAbs. Statistical analysis was performed using a mixed-effects repeated measures model with Dunnett's post-hoc multiple comparisons test (n = 12 animals on days 0-3 and n = 6 animals on days 4-7). Error bars represent mean ± SD. Bars indicate median ± interquartile range. *P < 0.05, **P < 0.01, *** P < 0.001, **** P < 0.0001; ns, not significant. [Figure 9]Combination of fusion peptide and stem helix antibodies limits SARS-CoV-2-mediated pathology in hamsters. Body weight change in Syrian hamsters exposed to SARS-CoV-2 (BA.2) after prophylaxis with a cocktail of fusion peptide and stem helix mAbs. Bars indicate median ± interquartile range. [Figure 10] Table 1. Cross-reactive antibodies neutralize multiple human coronaviruses. Neutralization curves of cross-reactive antibodies with SARS-CoV-2 Wuhan-Hu-1, SARS-CoV-2 Omicron variant, SARS-CoV-1, MERS-CoV, and NL63 envelope-pseudotyped viruses. Curves are derived from a representative cross-reactive antibody. Error bars represent the mean with SEM, and the dotted line represents 50% neutralization. DETAILED DESCRIPTION OF THE INVENTION

[0014] array Nucleic acid and amino acid sequences are shown using standard abbreviations for nucleotide bases and three-letter codes for amino acids, as defined in 37 C.F.R. 1.822. Only one strand of each nucleic acid sequence is shown, but the complementary strand is understood to be included by any reference to the displayed strand. Complementarity-determining regions (CDRs) are identified for each variable heavy chain domain (VH) shown below. H ) and in bold in the variable light chain domain (VL). a) SEQ ID NO: 1 is COV89-22 V H SEQ ID NOs: 2, 3, and 4 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 5 is COV89-22V L SEQ ID NOs: 6, 7, and 8 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] b) SEQ ID NO: 9 is COV44-62 V H SEQ ID NOs: 10, 11 and 12 are the amino acid sequences of HCDR1, HCDR2 and HCDR3, respectively. [ka] SEQ ID NO: 13 is COV44-62 V L SEQ ID NOs: 14, 15, and 16 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] c) SEQ ID NO: 17 is COV44-79 V H SEQ ID NOs: 18, 19, and 20 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 21 is COV44-79 V L SEQ ID NOs: 22, 23, and 24 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] d) SEQ ID NO: 25 is COV30-14 V H SEQ ID NOs: 26, 27, and 28 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 29 is COV30-14 V L SEQ ID NOs: 30, 31, and 32 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] e) SEQ ID NO: 33 is COV72-37 V H SEQ ID NOs: 34, 35, and 36 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 37 is COV72-37 V L SEQ ID NOs: 38, 39, and 40 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] f) SEQ ID NO: 41 is COV93-03 V H SEQ ID NOs: 42, 43, and 44 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 45 is COV93-03 V L SEQ ID NOs: 46, 47, and 48 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] g) SEQ ID NO: 49 is COV91-27 V H SEQ ID NOs: 50, 51, and 52 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 53 is COV91-27 V L SEQ ID NOs: 54, 55, and 56 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] h) SEQ ID NO: 57 is COV49-51 V H SEQ ID NOs: 58, 59, and 60 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 61 is COV49-51 V L SEQ ID NOs: 62, 63, and 64 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] i) SEQ ID NO: 65 is COV44-74 V H SEQ ID NOs: 66, 67, and 68 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 69 is COV44-74 V L SEQ ID NOs: 70, 71, and 72 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] j) SEQ ID NO: 73 is COV44-56 V H SEQ ID NOs: 74, 75, and 76 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 77 is COV44-56 V L SEQ ID NOs: 78, 79, and 80 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] k) SEQ ID NO: 81 is COV44-26 V H SEQ ID NOs: 82, 83, and 84 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 85 is COV44-26 V L SEQ ID NOs: 86, 87, and 88 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] l) SEQ ID NO: 89 is COV44-54 V H SEQ ID NOs: 90, 91, and 92 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 93 is COV44-54 V L SEQ ID NOs: 94, 95, and 96 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] m) SEQ ID NO: 97 is COV23-01 V H SEQ ID NOs: 98, 99, and 100 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 101 is COV23-01 V L SEQ ID NOs: 102, 103, and 104 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] n) SEQ ID NO: 105 is COV49-03 V H SEQ ID NOs: 106, 107, and 108 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 109 is COV49-03 V L SEQ ID NOs: 110, 111, and 112 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] o) SEQ ID NO: 113 is COV49-04 V H SEQ ID NOs: 114, 115, and 116 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 117 is COV49-04 V L SEQ ID NOs: 118, 119, and 120 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] p) SEQ ID NO: 121 is COV49-05 V H SEQ ID NOs: 122, 123, and 124 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 125 is COV49-05 V L SEQ ID NOs: 126, 127, and 128 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] q) SEQ ID NO: 129 is COV49-06 V H SEQ ID NOs: 130, 131, and 132 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 133 is COV49-06 V L SEQ ID NOs: 134, 135, and 136 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] r) SEQ ID NO: 137 is COV49-07 V H SEQ ID NOs: 138, 139, and 140 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 141 is COV49-07 V L SEQ ID NOs: 142, 143, and 144 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] s) SEQ ID NO: 145 is COV49-18 V H SEQ ID NOs: 146, 147, and 148 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 149 is COV49-18 V L SEQ ID NOs: 150, 151, and 152 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] t) SEQ ID NO: 153 is COV49-23 V H SEQ ID NOs: 154, 155, and 156 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 157 is COV49-23 V L SEQ ID NOs: 158, 159, and 160 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] u) SEQ ID NO: 161 is COV49-28 V H SEQ ID NOs: 162, 163, and 164 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 165 is COV49-28 V L SEQ ID NOs: 166, 167, and 168 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] v) SEQ ID NO: 169 is COV49-30 V H SEQ ID NOs: 170, 171, and 172 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 173 is COV49-30 V L SEQ ID NOs: 174, 175, and 176 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] w) SEQ ID NO: 177 is COV49-33 V H SEQ ID NOs: 178, 179, and 180 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 181 is COV49-33 V L SEQ ID NOs: 182, 183, and 184 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] x) SEQ ID NO: 185 is COV49-42 V H SEQ ID NOs: 186, 187, and 188 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 189 is COV49-42 V L SEQ ID NOs: 190, 191, and 192 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] y) SEQ ID NO: 193 is COV49-47 V H SEQ ID NOs: 194, 195, and 196 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 197 is COV49-47 V L SEQ ID NOs: 198, 199, and 200 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] z) SEQ ID NO: 201 is COV49-54 V H SEQ ID NOs: 202, 203, and 204 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 205 is COV49-54 V L SEQ ID NOs: 206, 207, and 208 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] aa) SEQ ID NO: 209 is COV57-01 V H SEQ ID NOs: 210, 211, and 212 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 213 is COV57-01 V L SEQ ID NOs: 214, 215, and 216 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] bb) SEQ ID NO: 217 is COV57-03 V H SEQ ID NOs: 218, 219, and 220 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 221 is COV57-03 V L SEQ ID NOs: 222, 223, and 224 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] cc) SEQ ID NO: 225 is COV57-04 V H SEQ ID NOs: 226, 227, and 228 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 229 is COV57-04 V L SEQ ID NOs: 230, 231, and 232 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] dd) SEQ ID NO: 233 is COV57-05 V H SEQ ID NOs: 234, 235, and 236 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 237 is COV57-05 V L SEQ ID NOs: 238, 239, and 240 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] ee) SEQ ID NO: 241 is COV57-13 V H SEQ ID NOs: 242, 243, and 244 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 245 is COV57-13 V L SEQ ID NOs: 246, 247, and 248 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] ff) SEQ ID NO: 249 is the COV57-19 V H SEQ ID NOs: 250, 251, and 252 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 253 is COV57-19 V L SEQ ID NOs: 254, 255, and 256 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] gg) SEQ ID NO: 257 is COV57-34 V H SEQ ID NOs: 258, 259, and 260 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 261 is COV57-34 V L SEQ ID NOs: 262, 263, and 264 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] hh) SEQ ID NO: 265 is COV57-38 V H SEQ ID NOs: 266, 267, and 268 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 269 is COV57-38 V LSEQ ID NOs: 270, 271, and 272 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] ii) SEQ ID NO: 273 is COV57-45 V H SEQ ID NOs: 274, 275, and 276 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 277 is COV57-45 V L SEQ ID NOs: 278, 279, and 280 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] jj) SEQ ID NO: 281 is COV77-02 V H SEQ ID NOs: 282, 283, and 284 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 285 is COV77-02 V L SEQ ID NOs: 286, 287, and 288 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] kk) SEQ ID NO: 289 is COV77-04 V H SEQ ID NOs: 290, 291, and 292 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 293 is COV77-04 VL SEQ ID NOs: 294, 295, and 296 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] ll) SEQ ID NO: 297 is COV77-05 V H SEQ ID NOs: 298, 299, and 300 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 301 is COV77-05 V L SEQ ID NOs: 302, 303, and 304 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] mm) SEQ ID NO: 305 is COV77-09 V H SEQ ID NOs: 306, 307, and 308 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 309 is COV77-09 V L SEQ ID NOs: 310, 311, and 312 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] nn) SEQ ID NO: 313 is COV77-14 V H SEQ ID NOs: 314, 315, and 316 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 317 is COV77-14 V L SEQ ID NOs: 318, 319, and 320 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] oo) SEQ ID NO: 321 is COV77-35 V H SEQ ID NOs: 322, 323, and 324 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 325 is COV77-35 V L SEQ ID NOs: 326, 327, and 328 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] pp) SEQ ID NO: 329 is COV77-39 V H SEQ ID NOs: 330, 331, and 332 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 333 is COV77-39 V L SEQ ID NOs: 334, 335, and 336 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] qq) SEQ ID NO: 337 is COV77-42 V H SEQ ID NOs: 338, 339, and 340 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 341 is COV77-42 V L SEQ ID NOs: 342, 343, and 344 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] rr) SEQ ID NO: 345 is COV77-43 V H SEQ ID NOs: 346, 347, and 348 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 349 is COV77-43 V L SEQ ID NOs: 350, 351, and 352 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] ss) SEQ ID NO: 353 is COV77-46 V H SEQ ID NOs: 354, 355, and 356 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 357 is COV77-46 V L SEQ ID NOs: 358, 359, and 360 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] tt) SEQ ID NO: 361 is COV77-76 V H SEQ ID NOs: 362, 363, and 364 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 365 is COV77-76 V L SEQ ID NOs: 366, 367, and 368 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] uu) SEQ ID NO: 369 is COV93-04 V H SEQ ID NOs: 370, 371, and 372 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 373 is COV93-04 V L SEQ ID NOs: 374, 375, and 376 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] vv) SEQ ID NO: 377 is COV93-08 V H SEQ ID NOs: 378, 379, and 380 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 381 is COV93-08 V L SEQ ID NOs: 382, ​​383, and 384 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] ww) SEQ ID NO: 385 is COV93-17 V H SEQ ID NOs: 386, 387, and 388 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 389 is COV93-17 V L SEQ ID NOs: 390, 391, and 392 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] xx) SEQ ID NO: 393 is COV93-18 V H SEQ ID NOs: 394, 395, and 396 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 397 is COV93-18 V L SEQ ID NOs: 398, 399, and 400 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] yy) SEQ ID NO: 401 is COV93-23 V H SEQ ID NOs: 402, 403, and 404 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 405 is COV93-23 V L SEQ ID NOs: 406, 407, and 408 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] zz) SEQ ID NO: 409 is COV78-36 V H SEQ ID NOs: 410, 411, and 412 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 413 is COV78-36 V L SEQ ID NOs: 414, 415, and 416 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] aaa) SEQ ID NO: 417 is COV93-38 V H SEQ ID NOs: 418, 419, and 420 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 421 is COV93-38 V L SEQ ID NOs: 422, 423, and 424 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] bbb) SEQ ID NO: 425 is COV93-60 V H SEQ ID NOs: 426, 427, and 428 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 429 is COV93-60 V L SEQ ID NOs: 430, 431, and 432 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] ccc) SEQ ID NO: 433 is COV93-61 V H SEQ ID NOs: 434, 435, and 436 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 437 is COV93-61 V L SEQ ID NOs: 438, 439, and 440 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] ddd) SEQ ID NO: 441 is COV89-03 V H SEQ ID NOs: 442, 443, and 444 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 445 is COV89-03 V L SEQ ID NOs: 446, 447, and 448 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] eee) SEQ ID NO: 449 is COV89-28 V H SEQ ID NOs: 450, 451, and 452 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 453 is COV89-28 V L SEQ ID NOs: 454, 455, and 456 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] fff) SEQ ID NO: 457 is COV30-35 V HSEQ ID NOs: 458, 459, and 460 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 461 is COV30-35 V L SEQ ID NOs: 462, 463, and 464 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] ggg) SEQ ID NO: 465 is COV30-80 V H SEQ ID NOs: 466, 467, and 468 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 469 is COV30-80 V L SEQ ID NOs: 470, 471, and 472 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] hhh) SEQ ID NO: 473 is COV44-25 V H SEQ ID NOs: 474, 475, and 476 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 477 is COV44-25 V L SEQ ID NOs: 478, 479, and 480 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] iii) SEQ ID NO: 481 is the sequence of COV44-37 VH SEQ ID NOs: 482, 483, and 484 are the amino acid sequences of HCDR1, HCDR2, and HCDR3, respectively. [ka] SEQ ID NO: 485 is COV44-37 V L SEQ ID NOs: 486, 487, and 488 are the amino acid sequences of LCDR1, LCDR2, and LCDR3, respectively. [ka] SEQ ID NOs: 489 and 490 are the amino acid sequences of the stem helix in the S2 domain of the coronavirus spike protein. LQPELDSFKEELDKYFKNHTS LDSFKEELDKYF SEQ ID NO: 491 is the amino acid sequence of peptide 42. PSKPSKRSFIEDLLF SEQ ID NO: 492 is the amino acid sequence of peptide 43. PSKRSFIEDLLFNKV SEQ ID NO: 493 is the amino acid sequence of peptide 44. RSFIEDLLFNKVTLA SEQ ID NO: 494 is the amino acid sequence of peptide 153. QPELDSFKEELDKYF SEQ ID NO: 495 is the amino acid sequence of peptide 154. LDSFKEELDKYFKNH SEQ ID NO: 496 is the amino acid sequence of peptide 155. FKEELDKYFKNHTSP SEQ ID NO: 497 is the amino acid sequence of the fusion peptide site (portion). SFIEDLLFNKVTLA SEQ ID NO: 498 is the amino acid sequence of the S2 peptide. RSFIEDLLF SEQ ID NOs: 499-532 are peptide sequences derived from coronavirus spike proteins and are shown in Figures 5C-5F.

[0015] Detailed Description of the Invention Disclosed herein are monoclonal antibodies and antigen-binding fragments thereof that specifically bind to the spike protein of SARS-CoV-2 and to the spike protein of at least one additional coronavirus, such as an alphacoronavirus or a betacoronavirus. In some embodiments, the monoclonal antibodies bind to the S2 domain of the spike protein. Bispecific antibodies are also disclosed. These monoclonal and bispecific antibodies can be used to inhibit coronavirus infection, including, but not limited to, SARS-CoV-2 infection. The monoclonal and bispecific antibodies can also be used to detect coronavirus infection.

[0016] I. Terminology Overview Unless otherwise specified, technical terms are used according to conventional usage. Definitions of many common terms in molecular biology can be found in Krebs et al. (eds.), Lewin's Genes XII, published by Jones & Bartlett Learning, 2017. As used herein, the singular forms "a," "an," and "the" refer to both the singular and the plural, unless the context clearly indicates otherwise. For example, the term "antigen" can include single or multiple antigens and can be considered equivalent to the phrase "at least one antigen." As used herein, the term "comprises" means "includes." Furthermore, unless otherwise indicated, it should be understood that any base size or amino acid size and any molecular weight or molecular mass value given for a nucleic acid or polypeptide is approximate and provided for illustrative purposes. While many methods and materials similar or equivalent to those described herein can be used, certain suitable methods and materials are described herein. In the event of conflict, the present specification, including explanations of terms, will control. Furthermore, the materials, methods, and examples are illustrative only and are not intended to be limiting. To facilitate review of the various embodiments, the following explanations of terms are provided:

[0017] About: Unless the context dictates otherwise, "about" refers to ±5% of the reference value. For example, "about" 100 refers to 95 to 105.

[0018] Administration: The introduction of an agent, such as a disclosed antibody, into a subject via a selected route. Administration can be local or systemic. For example, if the selected route is intravascular, the agent (e.g., antibody) is administered by introducing the composition into the subject's blood vessels. Exemplary administration routes include, but are not limited to, oral, injection (e.g., subcutaneous, intramuscular, intradermal, intraperitoneal, and intravenous), sublingual, rectal, transdermal (e.g., topical), intranasal, vaginal, and inhalation routes.

[0019] Amino acid substitution: The replacement of one amino acid in a polypeptide with a different amino acid.

[0020] Antibodies and antigen-binding fragments: Immunoglobulins, antigen-binding fragments, or derivatives thereof that specifically bind to and recognize an analyte (antigen), such as a coronavirus spike protein, such as the spike protein from SARS-CoV-2. The term "antibody" is used herein in the broadest sense and encompasses a variety of antibody structures, including, but not limited to, monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antigen-binding fragments, so long as they exhibit the desired antigen-binding activity.

[0021] Non-limiting examples of antibodies include, for example, intact immunoglobulins and variants and fragments thereof that retain binding affinity for an antigen. Antigen-binding fragments include those comprising the V H and V L and specifically binds to a cognate antigen. Examples of antibody fragments include, but are not limited to, Fv, Fab, Fab', Fab'-SH, F(ab')2; diabodies; linear antibodies; single-chain antibody molecules (e.g., scFv); and multispecific antibodies formed from antibody fragments. Antibody fragments include antigen-binding fragments produced by modification of whole antibodies or antigen-binding fragments synthesized de novo using recombinant DNA methods (see, e.g., Kontermann and Dubel (Eds), Antibody Engineering, Vols. 1-2, 2012). nd ed., Springer-Verlag, 2010).

[0022] Antibodies also include genetically engineered forms such as chimeric antibodies (such as humanized murine antibodies) and heteroconjugate antibodies (such as bispecific antibodies).

[0023] An antibody can have one or more binding sites. When multiple binding sites are present, the binding sites may be identical to one another or different. For example, naturally occurring immunoglobulins have two identical binding sites, single-chain antibodies or Fab fragments have one binding site, while bispecific or bifunctional antibodies have two different binding sites.

[0024] Typically, naturally occurring immunoglobulins have heavy (H) chains and light (L) chains interconnected by disulfide bonds. Immunoglobulin genes include the kappa, lambda, alpha, gamma, delta, epsilon, and mu constant region genes, as well as a wide variety of immunoglobulin variable domain genes. There are two types of light chains: lambda (λ) and kappa (κ). There are five major heavy chain classes (or isotypes) that determine the functional activity of antibody molecules: IgM, IgD, IgG, IgA, and IgE.

[0025] Each heavy and light chain contains a constant region (or constant domain) and a variable region (or variable domain). In combination, the heavy and light chain variable regions specifically bind to an antigen.

[0026] "V H References to "V" or "VH" refer to the variable region of an antibody heavy chain, including the variable region of an antigen-binding fragment such as an Fv, scFv, dsFv or Fab. L References to "VL" or "VL" refer to the variable domain of an antibody light chain, including the variable domain of an Fv, scFv, dsFv or Fab.

[0027] V H and V L are referred to as "complementarity determining regions" or "CDRs" (see, e.g., Kabat et al., Sequences of Proteins of Immunological Interest, 5 thed., NIH Publication No. 91-3242, Public Health Service, National Institutes of Health, USDapartment of Health and Human Services, 1991), comprise a "framework" region interrupted by three hypervariable regions, also called CDRs. The sequences of the framework regions of different light or heavy chains are relatively conserved within a species. The framework regions of an antibody, i.e., the combined framework regions of the constituent light and heavy chains, serve to position and align the CDRs in three-dimensional space.

[0028] CDRs are primarily responsible for binding to an epitope of an antigen. The amino acid sequence boundaries of a given CDR are determined by the amino acid sequence boundaries set forth in Kabat et al. (Sequences of Proteins of Immunological Interest, 5 thed., NIH Publication No. 91-3242, Public Health Service, National Institutes of Health, USDapartment of Health and Human Services, 1991; "Kabat" numbering scheme), Al-Lazikani et al. ("Standard conformations for the canonical structures of immunoglobulins," J. Mol. Biol., 273(4):927-948, 1997; "Chothia" numbering scheme), and Lefranc et al. ("IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains," Dev. Comp. Immunol., 27(1):55-77, 2003; "IMGT" numbering scheme). The CDRs of each chain are typically referred to as CDR1, CDR2, and CDR3 (N-terminus to C-terminus) and are also typically identified by the chain in which the particular CDR is located. Therefore, V H CDR3 is the V of the antibody in which it is found H CDR3 derived from V L CDR1 is the V of the antibody in which it is found L The light chain CDRs are sometimes referred to as LCDR1, LCDR2, and LCDR3. The heavy chain CDRs are sometimes referred to as HCDR1, HCDR2, and HCDR3.

[0029] In some embodiments, the disclosed antibodies comprise a heterologous constant domain, e.g., the antibody comprises a constant domain that is different from the native constant domain, e.g., a constant domain that includes one or more modifications to increase half-life (such as "LS" mutations).

[0030] A "monoclonal antibody" is an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical and / or bind the same epitope, except for variant antibodies that may contain, for example, naturally occurring mutations or arise during the generation of the monoclonal antibody preparation, and such variants are generally present in minor amounts. In contrast to polyclonal antibody preparations, which typically contain different antibodies directed against different determinants (epitopes), each monoclonal antibody of a monoclonal antibody preparation is directed against a single determinant on an antigen. Thus, the modifier "monoclonal" indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies and should not be construed as requiring production of the antibody by any particular method. For example, monoclonal antibodies can be produced by a variety of techniques, including, but not limited to, hybridoma methods, recombinant DNA methods, phage display methods, and methods utilizing transgenic animals containing all or part of the human immunoglobulin loci, as well as other exemplary methods for producing monoclonal antibodies described herein. In some examples, the monoclonal antibody is isolated from a subject. Monoclonal antibodies may have conservative amino acid substitutions that do not substantially affect antigen binding or other immunoglobulin functions. (See, e.g., Greenfield (Ed.), Antibodies: A Laboratory Manual, 2002.) nd (ed. New York: Cold Spring Harbor Laboratory Press, 2014).

[0031] A "humanized" antibody or antigen-binding fragment comprises a human framework region and one or more CDRs derived from a non-human (e.g., mouse, rat, or synthetic) antibody or antigen-binding fragment. The non-human antibody or antigen-binding fragment providing the CDRs is referred to as the "donor," and the human antibody or antigen-binding fragment providing the framework is referred to as the "acceptor." In one embodiment, all CDRs are derived from the donor immunoglobulin in the humanized immunoglobulin. Constant regions need not be present, but if present, they can be substantially identical to human immunoglobulin constant regions, e.g., at least about 85-90%, e.g., about 95% or more identical. Thus, all portions of a humanized antibody or antigen-binding fragment, except possibly for the CDRs, are substantially identical to the corresponding portions of a natural human antibody sequence.

[0032] A "chimeric antibody" is an antibody that contains sequences derived from two different antibodies, typically from different species. In some instances, a chimeric antibody contains one or more CDRs and / or framework regions from one human antibody and CDRs and / or framework regions from another human antibody.

[0033] A "fully human antibody" or "human antibody" is an antibody that contains sequences from (or derived from) the human genome and no sequences from another species. In some embodiments, a human antibody contains CDRs, framework regions, and (if present) an Fc region from (or derived from) the human genome. Human antibodies can be generated using techniques to generate antibodies based on sequences from the human genome, such as by phage display or in transgenic animals (see, e.g., Barbas et al., Phage Display: A Laboratory Manuel. 1). stEd. New York: Cold Spring Harbor Laboratory Press, 2004. Print.; Lonberg, Nat. Biotech., 23:1117-1125, 2005; Lonenberg, Curr. Opin. Immunol., 20:450-459, 2008).

[0034] Coronavirus-neutralizing antibody or antigen-binding fragment: An antibody or antigen-binding fragment that specifically binds to a coronavirus antigen (such as a spike protein) in a manner that inhibits infection or inhibits a biological function associated with the coronavirus. The antibody can neutralize one or more coronavirus activities. For example, a coronavirus-neutralizing antibody or antigen-binding fragment, such as SARS-CoV-2, can interfere with the virus by directly binding to the virus and limiting its entry into cells. Alternatively, the antibody can interfere with one or more post-attachment interactions between the pathogen and a receptor, for example, by using the receptor to block viral entry. In some examples, an antibody specific for a coronavirus spike protein neutralizes the infectious titer of the coronavirus.

[0035] In some embodiments, an antibody or antigen-binding fragment that specifically binds to and neutralizes coronavirus inhibits infection of cells, for example, by at least 50%, compared to a control antibody or antigen-binding fragment.

[0036] A "broadly neutralizing antibody" is an antibody that binds to and inhibits the function of related antigens, e.g., antigens that share at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% of the antigen's identical antigenic surface. With respect to antigens from pathogens such as viruses, the antibody can bind to and inhibit the function of antigens from more than one class and / or subclass of the pathogen. For example, with respect to coronaviruses, the antibody can bind to and inhibit the function of antigens such as spike proteins from coronaviruses.

[0037] Biological sample: A sample obtained from a subject. Biological samples include all clinical samples useful for detecting disease or infection in a subject, including, but not limited to, cells, tissues, and bodily fluids (blood, blood derivatives and fractions (such as serum), cerebrospinal fluid, etc.); and biopsy or surgically removed tissues, for example, tissues that are unfixed, frozen, or fixed in formalin or paraffin. In certain examples, biological samples are obtained from subjects with or suspected of having a coronavirus infection (such as, but not limited to, a SARS-CoV-2 infection).

[0038] Bispecific antibodies: Recombinant molecules composed of two different antigen-binding domains that consequently bind to two different antigen epitopes. Bispecific antibodies include molecules in which two antigen-binding domains are chemically or genetically linked. The antigen-binding domains may be linked using a linker. The antigen-binding domains may be monoclonal antibodies, antigen-binding fragments (e.g., Fab, scFv), or combinations thereof. Bispecific antibodies may contain one or more constant domains, but do not necessarily contain a constant domain.

[0039] Conditions sufficient to form an immune complex: Conditions that allow an antibody or antigen-binding fragment to bind to its cognate epitope to a degree detectably greater than binding to substantially all other epitopes and / or to the substantial exclusion of binding to substantially all other epitopes. Conditions sufficient to form an immune complex depend on the format of the binding reaction and are typically conditions utilized in immunoassay protocols or conditions encountered in vivo. For a description of immunoassay formats and conditions, see Greenfield (Ed.), Antibodies: A Laboratory Manual, 2002. nded. New York: Cold Spring Harbor Laboratory Press, 2014. The conditions used in this method are "physiological conditions," which includes reference to conditions (e.g., temperature, osmolarity, pH) typical inside a living mammal or mammalian cell. While it is recognized that some organs are exposed to extreme conditions, the in vivo and intracellular environment is typically near pH 7 (e.g., pH 6.0 to pH 8.0, more typically pH 6.5 to pH 7.5), contains water as the primary solvent, and exists at temperatures above 0°C and below 50°C. The osmolarity is within a range that supports cell viability and proliferation.

[0040] Immune complex formation can be detected by conventional methods, such as immunohistochemistry (IHC), immunoprecipitation (IP), flow cytometry, immunofluorescence microscopy, ELISA, immunoblotting (e.g., Western blot), magnetic resonance imaging (MRI), computed tomography (CT) scanning, radiography, and affinity chromatography.

[0041] Conjugate: A complex of two molecules linked to each other, e.g., covalently linked. In one embodiment, an antibody is linked to an effector molecule; e.g., an antibody that specifically binds to one or more coronaviruses, such as SARS-CoV-2, covalently linked to an effector molecule, such as a detectable label. Linkage can be by chemical or recombinant means. In one embodiment, linkage is chemical, where reaction between the antibody moiety and the effector molecule generates a covalent bond formed between the two molecules to form one molecule. A peptide linker (a short peptide sequence) can optionally be included between the antibody and the effector molecule. Conjugates are sometimes called "chimeric molecules" because they can be prepared from two molecules with distinct functional groups, such as an antibody and an effector molecule.

[0042] Conservative variant: A "conservative" amino acid substitution is one that does not substantially affect or impair the function of a protein, such as the ability of the protein to interact with a target protein. For example, a coronavirus-specific antibody can contain up to 1, 2, 3, 4, 5, 6, 7, 8, 9, or up to 10 conservative substitutions compared to a reference antibody sequence and retain specific binding activity and / or neutralizing activity against spike protein binding. The term "conservative variation" also includes the use of a substituted amino acid in place of an unsubstituted parent amino acid.

[0043] Substitutions, deletions, or additions that alter, add, or delete a single amino acid or a small percentage of amino acids (e.g., less than 5%, in some embodiments less than 1%) in an individual encoded sequence are conservative mutations in which the alteration results in the replacement of an amino acid with a chemically similar amino acid.

[0044] The following six groups are examples of amino acids that are considered conservative substitutions for one another: 1) alanine (A), serine (S), threonine (T); 2) aspartic acid (D), glutamic acid (E); 3) asparagine (N), glutamine (Q); 4) arginine (R), lysine (K); 5) isoleucine (I), leucine (L), methionine (M), valine (V); and 6) Phenylalanine (F), tyrosine (Y), tryptophan (W).

[0045] Non-conservative substitutions reduce the activity or function of an antibody, for example, its ability to specifically bind to a coronavirus spike protein. For example, if an amino acid residue is essential for the function of a protein, an otherwise conservative substitution may inhibit its activity. Therefore, conservative substitutions do not alter the basic function of the protein of interest.

[0046] Contact: Placement in direct physical association; including both solid and liquid forms that can occur either in vivo or in vitro. Contact includes contact between one molecule and another molecule, for example, amino acids on the surface of one polypeptide, such as an antigen, that contacts another polypeptide, such as an antibody. Contact can also include contacting cells, for example, by directly physically associating an antibody with the cell.

[0047] Control: Reference standard. In some embodiments, the control is a negative control, such as a sample obtained from a healthy patient not infected with coronavirus. In other embodiments, the control is a positive control, such as a sample obtained from a patient diagnosed with coronavirus infection. In still other embodiments, the control is a historical control or standard reference value or range of values ​​(e.g., previously tested control samples, e.g., a group of patients with a known prognosis or outcome, or a group of samples representing baseline or normal values).

[0048] The difference between test sample and control can be increased or decreased.This difference can be qualitative or quantitative, and can be, for example, statistically significant.In some examples, this difference is at least about 5%, for example, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 100%, at least about 150%, at least about 200%, at least about 250%, at least about 300%, at least about 350%, at least about 400%, or at least about 500% increase or decrease compared to control.

[0049] Coronavirus: A family of single-stranded, positive-stranded RNA viruses known to cause severe respiratory disease. Viruses within the Coronaviridae family currently known to infect humans are derived from the genera Alphacoronavirus and Betacoronavirus. Additionally, Gammacoronavirus and Deltacoronavirus are thought to be capable of infecting humans in the future.

[0050] Non-limiting examples of betacoronaviruses include SARS-CoV-2, Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), human coronavirus HKU1 (HKU1-CoV), human coronavirus OC43 (OC43-CoV), mouse hepatitis virus (MHV-CoV), bat SARS-like coronavirus WIV1 (WIV1-CoV), and human coronavirus HKU9 (HKU9-CoV). Non-limiting examples of alphacoronaviruses include human coronavirus 229E (229E-CoV), human coronavirus NL63 (NL63-CoV), porcine epidemic diarrhea virus (PEDV), and transmissible gastroenteritis coronavirus (TGEV). A non-limiting example of a deltacoronavirus is porcine deltacoronavirus (SDCV).

[0051] The viral genome is capped, polyadenylated, and surrounded by nucleocapsid proteins. Coronavirus virions contain a viral envelope containing a type I fusion glycoprotein called the spike (S) protein. Most coronaviruses share a common genome organization with a replicase gene.

[0052] Degenerate variant: In the context of this disclosure, a "degenerate variant" refers to a polynucleotide encoding a polypeptide (such as an antibody heavy or light chain) that comprises a sequence that is degenerate as a result of the genetic code. There are 20 natural amino acids, most of which are specified by one or more codons. Thus, all degenerate nucleotide sequences that encode a peptide are included, so long as the amino acid sequence of the peptide encoded by the nucleotide sequence remains unchanged.

[0053] Detectable marker: A detectable molecule (also known as a label) that is directly or indirectly conjugated to a second molecule, such as an antibody, to facilitate detection of the second molecule. For example, detectable markers can be detected by ELISA, spectrophotometry, flow cytometry, microscopy, or imaging techniques (CT scan, MRI, ultrasound, fiberoptic examination, laparoscopy, etc.). Specific, non-limiting examples of detectable markers include fluorophores, chemiluminescent agents, enzyme conjugates, radioisotopes, and heavy metals or compounds (e.g., superparamagnetic iron oxide nanocrystals for detection by MRI). Methods and guidelines for using detectable markers in selecting detectable markers suitable for various purposes can be found, for example, in Green and Sambrook (Molecular Cloning: A Laboratory Manual, 4 th ed., New York: Cold Spring Harbor Laboratory Press, 2012) and Ausubel et al. (Eds.) (Current Protocols in Molecular Biology, New York: John Wiley and Sons, including supplements, 2017).

[0054] Detect: To identify the existence, presence, or fact of something.

[0055] Effective amount: An amount sufficient to achieve a desired effect in a subject to which a particular substance is administered. For example, this may be the amount necessary to inhibit a coronavirus infection, such as a SARS-CoV-2 infection, or to measurably alter the outward symptoms of such an infection.

[0056] In one example, the desired response is to inhibit, reduce, or prevent SARS-CoV-2 infection. Complete elimination, reduction, or prevention of SARS-CoV-2 infection is not required for the method to be effective. For example, administration of an effective amount of an immunogen can induce an immune response that reduces SARS-CoV-2 infection (e.g., as measured by infection of cells or by the number or percentage of subjects infected with SARS-CoV-2) by a desired amount, e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, or even at least 100%, compared to an appropriate control (eliminating or preventing detectable SARS-CoV-2 infection). Use of the antibodies of the present disclosure can also result in inhibition of further coronavirus infection.

[0057] In some embodiments, administration of an effective amount of the disclosed antibodies or antigen-binding fragments that bind to the coronavirus spike protein can reduce or inhibit infection (e.g., as measured by infection of cells, by the number or percentage of subjects infected with the coronavirus, or by increased survival of infected subjects, or by a reduction in symptoms associated with the infection) by a desired amount, e.g., by at least 10%, at least 20%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, or even at least 100% (eliminating or preventing detectable infection) compared to a suitable control.

[0058] The effective amount of an antibody or antigen-binding fragment that specifically binds to a coronavirus spike protein to be administered to a subject to inhibit infection will vary depending on several factors related to the subject, such as the subject's overall health and / or weight. An effective amount can be determined by varying the dosage and measuring the resulting response, such as a reduction in pathogen titer. An effective amount can also be determined by various in vitro, in vivo, or in situ immunoassays.

[0059] Effective amount includes the partial dose that contributes to achieve effective response in combination with the previous or subsequent administration.For example, effective amount of drug can be administered in a single dose or in several doses, for example, every day, during a series of treatments that last for several days or weeks.However, effective amount can depend on the subject being treated, the severity and type of the condition being treated, and the mode of administration.The unit dosage form of drug can be packaged in a certain amount or multiple of effective amount, for example, in a vial (for example, with a pierceable cap) or syringe with sterile components.

[0060] Effector molecule: A molecule that has or is intended to produce a desired effect; for example, a desired effect on the cell that the effector molecule targets, or a detectable marker. Effector molecules can include, for example, polypeptides and small molecules. Some effector molecules can have or produce more than one desired effect.

[0061] Epitope: Antigenic determinant. These are specific chemical groups or peptide sequences on a molecule that are antigenic and therefore provoke a specific immune response; for example, an epitope is the region of an antigen to which B cells and / or T cells respond. An antibody can bind to a specific antigenic epitope, such as an epitope on the coronavirus spike protein.

[0062] Expression: The transcription or translation of a nucleic acid sequence. For example, a coding nucleic acid sequence (such as a gene) is expressed when its DNA is transcribed into RNA or an RNA fragment, which in some instances may be processed to become mRNA. A coding nucleic acid sequence (such as a gene) may also be expressed when its mRNA is translated into an amino acid sequence such as a protein or protein fragment. In certain instances, a heterologous gene is expressed when it is transcribed into RNA. In other instances, a heterologous gene is expressed when its RNA is translated into an amino acid sequence. Regulation of expression can include control by transcription, translation, RNA transport and processing, degradation of intermediate molecules such as mRNA, or activation, inactivation, compartmentalization, or degradation of specific protein molecules after they are produced.

[0063] Expression control sequence: A nucleic acid sequence that regulates the expression of a heterologous nucleic acid sequence to which it is operably linked. An expression control sequence is operably linked to a nucleic acid sequence if it controls and regulates the transcription and, if necessary, translation of the nucleic acid sequence. Thus, expression control sequences can include appropriate promoters, enhancers, transcription terminators, a start codon (ATG) in front of a protein-coding gene, splicing signals for introns, maintaining the correct reading frame of the gene to allow proper translation of mRNA, and stop codons. The term "control sequence" is intended to include at least components whose presence can affect expression, and may also include additional components whose presence is advantageous, such as leader sequences and fusion partner sequences. Expression control sequences can include a promoter.

[0064] Expression vector: A vector containing a recombinant polynucleotide comprising an expression control sequence operably linked to the nucleotide sequence to be expressed. An expression vector contains sufficient cis-acting elements for expression. Other elements for expression can be supplied by the host cell or in an in vitro expression system. Non-limiting examples of expression vectors include cosmids, plasmids (e.g., naked or contained in liposomes), and viruses (e.g., lentiviruses, retroviruses, adenoviruses, and adeno-associated viruses) that incorporate the recombinant polynucleotide.

[0065] The polynucleotide can be inserted into an expression vector containing a promoter sequence that promotes efficient transcription of the inserted gene sequence in the host. Expression vectors typically contain an origin of replication, a promoter, and specific nucleic acid sequences that allow for phenotypic selection of transformed cells.

[0066] Fc region: The constant region of an antibody excluding the first heavy chain constant domain. The Fc region generally refers to the last two heavy chain constant domains of IgA, IgD, and IgG, and the last three heavy chain constant domains of IgE and IgM. The Fc region may also include part or all of the flexible hinge N-terminal to these domains. In the case of IgA and IgM, the Fc region may or may not include the tailpiece and may or may not be connected by a J chain. In the case of IgG, the Fc region is typically understood to include immunoglobulin domains Cγ2 and Cγ3, and optionally the lower part of the hinge between Cγ1 and Cγ2. Although the boundaries of the Fc region can vary, the human IgG heavy chain Fc region is usually defined as including residues following C226 or P230 relative to the Fc carboxyl terminus, and numbering follows EU numbering. In the case of IgA, the Fc region comprises immunoglobulin domains Cα2 and Cα3, and optionally the lower part of the hinge between Cα1 and Cα2.

[0067] Heterologous: Derived from a different genetic source. A nucleic acid molecule heterologous to a cell derived from a genetic source other than the cell in which it is expressed. In one specific, non-limiting example, a heterologous nucleic acid molecule encoding a protein such as an scFv is expressed in a cell, such as a mammalian cell. Methods for introducing heterologous nucleic acid molecules into cells or organisms are well known in the art, such as electroporation, lipofection, particle gun acceleration, and nucleic acid transformation, including homologous recombination.

[0068] Host cell: A cell in which a vector can be propagated and its DNA expressed. The cell can be prokaryotic or eukaryotic. The term also includes any progeny of the subject host cell. It is understood that all progeny may not be identical to the parent cell because there may be mutations that occur during replication. However, such progeny are included when the term "host cell" is used.

[0069] IgA: A polypeptide belonging to a class of antibodies substantially encoded by recognized immunoglobulin alpha genes. In humans, this class or isotype includes IgA1 and IgA2. IgA antibodies can exist as monomers, polymers (primarily in dimeric form) (called pIgA), and secretory IgA. The constant chain of wild-type IgA contains an 18-amino acid extension at its C-terminus called the tailpiece (tp). Polymeric IgA is secreted by plasma cells along with a 15-kDa peptide called the J chain, which connects two IgA monomers via a conserved cysteine ​​residue in the tailpiece.

[0070] IgG: A polypeptide belonging to a class or isotype of antibody substantially encoded by recognized immunoglobulin gamma genes. In humans, this class includes IgG1, IgG2, IgG3, and IgG4.

[0071] Immune complex: The binding of an antibody or antigen-binding fragment (such as scFv) to a soluble antigen forms an immune complex. The formation of the immune complex can be detected by conventional methods, such as immunohistochemistry, immunoprecipitation, flow cytometry, immunofluorescence microscopy, ELISA, immunoblotting (e.g., Western blot), magnetic resonance imaging, CT scan, radiography, and affinity chromatography.

[0072] Suppressing or treating a disease: For example, suppressing the full development of a disease or condition in a subject at risk for a disease, such as a coronavirus infection. "Treatment" refers to a therapeutic intervention that ameliorates the symptoms or condition of a disease or pathological condition after it has begun to develop. The term "ameliorating," with respect to a disease or pathological condition, refers to any observable beneficial effect of the treatment. Suppressing a disease can include preventing or reducing the risk of disease, such as preventing or reducing the risk of viral infection. A beneficial effect can be evidenced, for example, by a delay in the onset of clinical symptoms of the disease in a susceptible subject, a reduction in the severity of some or all clinical symptoms of the disease, a delay in the progression of the disease, a reduction in viral load, an improvement in the overall health or well-being of the subject, or other parameters specific to a particular disease. A "prophylactic" treatment is a treatment administered to a subject who does not show signs of disease or who shows only early signs of the disease, with the intent of reducing the risk of developing the condition.

[0073] The term "reduce" is a relative term, such as when a disease or condition is quantitatively reduced after administration of the agent, or when a disease or condition is reduced after administration of the agent compared to a reference agent, the agent reduces the disease or condition.Similarly, the term "prevent" does not necessarily mean that the agent completely eliminates the disease or condition, as long as at least one characteristic of the disease or condition is eliminated.Thus, a composition that reduces or prevents infection can eliminate such infection, but not necessarily completely, as long as the infection is measurably reduced by at least about 50%, for example, at least about 70%, or about 80%, or even about 90%, for example, in the absence of the agent or compared to a reference agent.

[0074] Isolated: A separately produced or purified biological component (e.g., a nucleic acid, peptide, protein, or protein complex, such as an antibody) that is substantially separated from other biological components, i.e., other chromosomal and extrachromosomal DNA and RNA and proteins, in the cells of the organism in which the component naturally occurs. Thus, isolated nucleic acids, peptides, and proteins include nucleic acids and proteins purified by standard purification methods. The term also encompasses nucleic acids, peptides, and proteins prepared by recombinant expression in a host cell, as well as chemically synthesized nucleic acids. An isolated nucleic acid, peptide, or protein, such as an antibody, can be at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% pure.

[0075] Kabat location: Kabat et al. (Sequences of Proteins of Immunological Interest, 5 th The position of the residue in the amino acid sequence according to the numbering convention described by the National Institutes of Health, Bethesda, NIH Publication No. 91-3242, 1991).

[0076] Linker: A bifunctional molecule that can be used to link two molecules into one adjacent molecule, for example, to link a detectable marker to an antibody. Non-limiting examples of peptide linkers include glycine-serine linkers.

[0077] The terms "conjugating," "joining," "binding," or "linking" can refer to making two molecules into one contiguous molecule; for example, linking two polypeptides into one contiguous polypeptide, or covalently attaching an effector molecule or detectable marker radionuclide or other molecule to a polypeptide such as an scFv. Linking can be by either chemical or recombinant means. "Chemical means" refers to a reaction between an antibody moiety and an effector molecule such that a covalent bond is formed between the two molecules to form one molecule.

[0078] Nucleic acid (molecule or sequence): A deoxyribonucleotide or ribonucleotide polymer or combination thereof, including, but not limited to, cDNA, mRNA, genomic DNA, and synthetic (e.g., chemically synthesized) DNA or RNA. Nucleic acids can be double-stranded (ds) or single-stranded (ss). If single-stranded, the nucleic acid can be the sense strand or the antisense strand. Nucleic acids can include natural nucleotides (A, T / U, C, G, etc.) and can include analogs of natural nucleotides, such as labeled nucleotides.

[0079] "cDNA" refers to DNA that is complementary or identical to mRNA in either single- or double-stranded form.

[0080] "Encoding" refers to the inherent property of a particular sequence of nucleotides in a polynucleotide, such as a gene, cDNA, or mRNA, to serve as a template for the synthesis of other polymers and macromolecules in biological processes having either a defined sequence of nucleotides (i.e., rRNA, tRNA, and mRNA) or a defined sequence of amino acids, and the biological properties resulting therefrom. Thus, a gene encodes a protein if transcription and translation of the mRNA produced by that gene produces the protein in a cell or other biological system. Both the coding strand, whose nucleotide sequence is identical to the mRNA sequence and is usually provided in a sequence listing, and the non-coding strand used as a template for transcription of the gene or cDNA can be said to encode the protein or other product of that gene or cDNA. Unless otherwise specified, "nucleotide sequences encoding amino acid sequences" are degenerate versions of each other and include all nucleotide sequences that encode the same amino acid sequence. Protein- and RNA-encoding nucleotide sequences may contain introns.

[0081] Operably linked: A first nucleic acid sequence is operably linked to a second nucleic acid sequence when the first nucleic acid sequence is in a functional relationship with the second nucleic acid sequence. For example, a promoter, such as a CMV promoter, is operably linked to a coding sequence when it affects the transcription or expression of the coding sequence. Generally, operably linked DNA is contiguous and, where necessary to join two protein-coding regions, in the same reading frame.

[0082] Pharmaceutically acceptable carriers: Useful pharmaceutically acceptable carriers are conventional. Remington: The Science and Practice of Pharmacy, 22 nd ed., London, UK: Pharmaceutical Press, 2013, describes compositions and formulations suitable for pharmaceutical delivery of the disclosed agents.

[0083] Generally, the nature of the carrier will depend on the particular mode of administration being employed. For example, parenteral formulations typically comprise injectable fluids containing pharmaceutically and physiologically acceptable fluids such as water, physiological saline, balanced salt solution, aqueous dextrose, glycerol, or the like as excipients. For solid compositions (e.g., in the form of powders, pills, tablets, or capsules), conventional non-toxic solid carriers can include, for example, pharmaceutical grades of mannitol, lactose, starch, or magnesium stearate. In addition to biologically neutral carriers, the administered pharmaceutical composition may contain minor amounts of non-toxic auxiliary substances such as wetting or emulsifying agents, added preservatives (such as non-natural preservatives), and pH buffering agents, e.g., sodium acetate or sorbitan monolaurate. In certain instances, the pharmaceutically acceptable carrier is sterile and suitable for parenteral administration to a subject, e.g., by injection. In some embodiments, the active agent and the pharmaceutically acceptable carrier are provided in a unit dosage form, such as a pill, or in a selected amount in a vial. The unit dosage form may comprise one dose or multiple doses (eg, in a vial from which a metered dose of the agent may be selectively dispensed).

[0084] Polypeptide: A polymer in which the monomers are amino acid residues joined to each other by amide bonds. When the amino acids are alpha-amino acids, either the L-optical isomer or the D-optical isomer can be used, with the L-isomer being preferred. As used herein, the term "polypeptide" or "protein" is intended to encompass any amino acid sequence, including modified sequences such as glycoproteins. Polypeptides include both naturally occurring proteins and recombinantly or synthetically produced proteins. Polypeptides have an amino terminus (N-terminus) and a carboxy terminus. In some embodiments, the polypeptide is a disclosed antibody or fragment thereof.

[0085] Purified: The term "purified" does not require absolute purity but is intended to be a relative term. Thus, for example, a purified peptide preparation is one in which a peptide or protein (such as an antibody) is more enriched than the peptide or protein in its natural environment within a cell. In one embodiment, a preparation is purified such that the protein or peptide represents at least 50% of the total peptide or protein content of the preparation.

[0086] Recombinant: A recombinant nucleic acid is one that has a sequence that does not occur in nature or that has a sequence created by the artificial combination of two otherwise separated sequence segments. This artificial combination can be achieved by chemical synthesis or, more commonly, by the artificial manipulation of isolated segments of nucleic acid molecules, for example, by genetic engineering techniques. A recombinant protein is one that has a sequence that does not occur in nature or that has a sequence created by the artificial combination of two otherwise separated sequence segments. In some embodiments, a recombinant protein is encoded by a heterologous (e.g., recombinant) nucleic acid introduced into a host cell, such as a bacterial or eukaryotic cell. The nucleic acid can be introduced, for example, into an expression vector with a signal capable of expressing the protein encoded by the introduced nucleic acid, or the nucleic acid can be integrated into a host cell chromosome.

[0087] SARS-CoV-2: SARS-CoV-2, also known as the Wuhan coronavirus or 2019 novel coronavirus, is a single-stranded, positive-stranded RNA virus of the Betacoronavirus genus that has emerged as a highly lethal cause of severe acute respiratory infection. The viral genome is capped, polyadenylated, and enclosed by a nucleocapsid protein. SARS-CoV-2 virions contain a viral envelope with a large spike glycoprotein. Similar to most coronaviruses, the SARS-CoV-2 genome shares a common genome organization with replicase genes in the 5'-2 / 3 of the genome and structural genes in the 3'-1 / 3 of the genome. The SARS-CoV-2 genome encodes a canonical set of structural protein genes in the following order: 5'-spike (S)-envelope (E)-membrane (M) and nucleocapsid (N)-3'. Symptoms of SARS-CoV-2 infection include fever and respiratory illness, such as dry cough and shortness of breath. Severe cases of infection can progress to severe pneumonia, multiple organ failure, and death. The time from exposure to symptom onset is approximately 2 to 14 days.

[0088] Standard methods for detecting viral infections can be used to detect SARS-CoV-2 infection, including, but not limited to, evaluation of patient symptoms and background and genetic testing such as reverse transcription polymerase chain reaction (rRT-PCR). Testing can be performed on patient samples, such as respiratory or blood samples.

[0089] Spike (S) protein (coronavirus): Class I fusion glycoproteins are initially synthesized as precursor proteins approximately 1256 amino acids in size for SARS-CoV and 1273 amino acids in size for SARS-CoV-2. Individual precursor S polypeptides form homotrimers and undergo glycosylation in the Golgi apparatus, processing to remove the signal peptide, and cleavage by cellular proteases between approximately positions 679 / 680 for SARS-CoV and 685 / 686 for SARS-CoV-2 to generate separate S1 and S2 polypeptide chains, which remain associated as S1 / S2 protomers within the homotrimer, thus forming a trimer of heterodimers. The S1 subunit is distal to the viral membrane and contains the receptor-binding domain (RBD), which is thought to mediate viral attachment to its host receptor. The S2 subunit contains the fusion protein machinery, including the fusion peptide, two heptad repeat sequences (HR1 and HR2) and a central helix typical of fusion glycoproteins, a transmembrane domain, and a cytosolic tail domain.

[0090] An exemplary sequence of a SARS-CoV S protein is provided in GENBANK® GI:30795145, available on February 1, 2022. An exemplary sequence of a HKU1-CoV S protein is provided in GENBANK® GI:123867264, available on February 1, 2022. An exemplary sequence of an OC43-CoV S protein is provided in GENBANK® GI:744516696, available on February 1, 2022. An exemplary sequence of an NL63-CoV S protein is provided in GENBANK® GI:71153773, available on February 1, 2022. An exemplary sequence of a 229E-CoV S protein is provided in GENBANK® GI:1060650120, available on February 1, 2022. The S protein contains both an S1 domain and an S2 domain.

[0091] The numbering used in the disclosed SARS-CoV-2 S protein and fragments thereof is for the S protein of SARS-CoV-2, the sequence of which was deposited under NCBI reference number YP_009724390.1, available on February 1, 2022, and which is incorporated herein by reference in its entirety.

[0092] Sequence identity: The identity between two or more nucleic acid sequences or two or more amino acid sequences is expressed in terms of the percentage of identity between the sequences. Sequence identity can be measured in terms of the percentage of identity. The higher the percentage, the more identical the sequences are. The V of an antibody that specifically binds to a target antigen L or V H Homologs and variants of are typically characterized by having at least about 75% sequence identity, e.g., at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity, counted over the full length alignment with the amino acid sequence of interest.

[0093] Any suitable method can be used to align sequences for comparison. Non-limiting examples of programs and alignment algorithms include those described by Smith and Waterman, Adv. Appl. Math. 2(4):482-489, 1981; Needleman and Wunsch, J. Mol. Biol. 48(3):443-453, 1970; Pearson and Lipman, Proc. Natl. Acad. Sci. USA 85(8):2444-2448, 1988; Higgins and Sharp, Gene, 73(1):237-244, 1988; Higgins and Sharp, Bioinformatics, 5(2):151-3, 1989; Corpet, Nucleic Acids Res. 16(22):10881-10890, 1988; Huang et al., Bioinformatics, 8(2):155-165, 1992; and Pearson, Methods Mol. Biol. 24:307-331, 1994., Altschul et al., J. Mol. Biol. 215(3):403-410, 1990, which present a detailed discussion of sequence alignment methods and homology calculations. The NCBI Basic Local Alignment Search Tool (BLAST) (Altschul et al., J. Mol. Biol. 215(3):403-410, 1990) is available from several sources, including the National Center for Biological Information and the internet, for use in conjunction with the sequence analysis programs blastp, blastn, blastx, tblastn, and tblastx. Blastn is used to compare nucleic acid sequences, and blastp is used to compare amino acid sequences. Further information can be found on the NCBI website.

[0094] Generally, when two sequences are aligned, the number of matches is determined by counting the number of positions where the same nucleotide or amino acid residue exists in both sequences. The percent sequence identity between two sequences is determined by dividing the number of matches by the length or concatenated length of the sequence described in the identified sequence (for example, 100 consecutive nucleotides or amino acid residues from the sequence described in the identified sequence), and then multiplying the result by 100.

[0095] Specifically binds: When referring to an antibody or antigen-binding fragment, this refers to a binding reaction that determines the presence of a target protein in the presence of a heterogeneous population of proteins and other biological agents. Thus, under specified conditions, an antibody will preferentially bind to a specific target protein, peptide, or polysaccharide (e.g., an antigen present on the surface of a pathogen, e.g., a coronavirus spike protein) and will not bind in significant amounts to other proteins present in a sample or subject. With respect to spike proteins, epitopes may be present on the spike proteins of more than one coronavirus such that an antibody will bind to the spike protein on more than one virus but not to other proteins, such as proteins from other viruses or other (non-spike) proteins of the coronavirus. Specific binding can be determined by standard methods. See Harlow & Lane, Antibodies, A Laboratory Manual, 2014, for a description of immunoassay formats and conditions that can be used to measure specific immune reactivity. nd ed. Cold Spring Harbor Publications, New York (2013).

[0096] For antibody-antigen complexes, the specific binding between the antigen and the antibody is approximately 10 -7 Less than molar, e.g., about 10 -8 Less than 10 molar -9 Less than molar, or even about 10 -10 Less than molar K D K Drefers to the dissociation constant of a given interaction, such as a polypeptide-ligand interaction or an antibody-antigen interaction. For example, in the case of a bimolecular interaction between an antibody or antigen-binding fragment and an antigen, it is the concentration of the individual components of the bimolecular interaction divided by the concentration of the complex.

[0097] Antibodies that specifically bind to an epitope on the coronavirus spike protein, such as the S domain, RBD domain, or NTD domain, can bind to molecules or drugs containing this domain, including viruses, substrates to which the spike protein is attached, or proteins in biological samples. It is recognized, of course, that some degree of nonspecific interaction between the antibody and non-targets may occur. Specific binding typically results in a much stronger association between the antibody and the spike protein than between antibodies from other, different coronavirus proteins (e.g., E, M, or N proteins) or non-coronavirus proteins. Specific binding typically results in a greater than two-fold, e.g., greater than five-fold, greater than ten-fold, or greater than one hundred-fold increase in the amount of antibody bound (per unit time) to a protein containing the target epitope or to cells or tissues expressing the target epitope compared to proteins, cells, or tissues lacking this epitope. Specific binding to a protein under such conditions requires an antibody selected for its specificity for a particular protein. A variety of immunoassay formats are appropriate for selecting antibodies or other ligands specifically immunoreactive with a particular protein. For example, solid-phase ELISA immunoassays are routinely used to select monoclonal antibodies specifically immunoreactive with a protein.

[0098] Subject: Living multicellular vertebrate organisms, a category that includes humans and non-human mammals, such as non-human primates, pigs, camels, bats, sheep, cows, dogs, cats, and rodents. In one example, the subject is a human. In a particular example, the subject is a human. In a further example, a subject in need of inhibition of SARS-CoV-2 infection is selected. For example, the subject is either uninfected and at risk for SARS-CoV-2 infection, or infected and in need of treatment.

[0099] Transformed: A transformed cell is a cell into which a nucleic acid molecule has been introduced by molecular biology techniques. As used herein, the term transformation and the like (e.g., transformation, transfection, transduction, etc.) encompasses all techniques by which a nucleic acid molecule can be introduced into such a cell, including transduction by viral vector, transformation by plasmid vector, and introduction of DNA by electroporation, lipofection, and particle gun acceleration.

[0100] Vector: An entity containing a nucleic acid molecule (such as a DNA or RNA molecule) operably linked to a coding sequence for a protein of interest and having a promoter(s) capable of expressing the coding sequence. Non-limiting examples include naked or packaged (lipid and / or protein) DNA, naked or packaged RNA, a subcomponent of a virus or bacteria or other microorganism that may be replication-incompetent, or a virus or bacteria or other microorganism that may be replication-competent. A vector is sometimes referred to as a construct. A recombinant DNA vector is a vector that contains recombinant DNA. A vector may contain a nucleic acid sequence that enables replication in a host cell, such as an origin of replication. A vector may also contain one or more selectable marker genes and other genetic elements. A viral vector is a recombinant nucleic acid vector that contains at least some nucleic acid sequences derived from one or more viruses. In some embodiments, the viral vector contains a nucleic acid molecule encoding the disclosed antibody or antigen-binding fragment that specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the viral vector may be an adeno-associated virus (AAV) vector.

[0101] Under conditions sufficient for: A phrase used to describe any environment that allows for a desired activity.

[0102] II. DESCRIPTION OF EMBODIMENTS Isolated monoclonal antibodies and antigen-binding fragments that specifically bind to coronavirus spike proteins are provided. The monoclonal antibodies and antigen-binding fragments specifically bind to coronavirus spike proteins and neutralize SARS-CoV-2 and at least one additional betacoronavirus or alphacoronavirus. The antibodies and antigen-binding fragments can be fully human. The antibodies and antigen-binding fragments can neutralize coronaviruses, including, but not limited to, SARS-CoV-2. In some embodiments, the disclosed antibodies can inhibit coronavirus infection in vivo and can be administered before or after infection with a coronavirus, such as, but not limited to, SARS-CoV-2. Bispecific antibodies comprising the variable domains of these antibodies are also provided. Additionally, compositions comprising the antibodies and antigen-binding fragments and a pharmaceutically acceptable carrier are disclosed herein. Nucleic acids encoding the antibodies, antigen-binding fragments, variable domains, and expression vectors (such as adeno-associated virus (AAV) virus vectors) comprising these nucleic acids are also provided. The antibodies, antigen-binding fragments, nucleic acid molecules, host cells, and compositions can be used for research, diagnostic, treatment, and prophylactic purposes. For example, the disclosed antibodies and antigen-binding fragments can be used to diagnose a subject with a coronavirus infection or can be administered to inhibit a coronavirus infection in a subject.

[0103] A. Monoclonal antibodies and antigen-binding fragments thereof that specifically bind to coronavirus spike proteins The following discussion of monoclonal antibodies refers to isolated monoclonal antibodies comprising heavy and / or light chain variable domains (or antigen-binding fragments thereof) comprising CDR1, CDR2, and / or CDR3 in accordance with the IMGT numbering scheme (unless the context indicates otherwise). Various CDR numbering schemes (e.g., Kabat, Chothia, or IMGT numbering schemes) can be used to determine the CDR positions. The amino acid sequences of the heavy and light chains and CDRs of the disclosed monoclonal antibodies according to the IMGT numbering scheme are provided in the sequence listings, but are for illustrative purposes only.

[0104] In some embodiments, a monoclonal antibody is provided that comprises the heavy chain CDRs and light chain CDRs of any one of the antibodies described herein. In some embodiments, a monoclonal antibody is provided that comprises the heavy chain variable region and light chain variable region of any one of the antibodies described herein.

[0105] In some embodiments, the antibody binds to the N-terminal domain of the coronavirus spike protein. In other embodiments, the antibody binds to the S domain of the coronavirus spike protein. In further embodiments, the antibody binds to the stem helix of the S2 domain of the spike protein, e.g., LQPELDSFKEELDKYFKNHTS (SEQ ID NO: 489), e.g., LDSFKEELDKYF (SEQ ID NO: 490).

[0106] In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43. In other embodiments, the antibody or antigen-binding fragment neutralizes betacoronaviruses and alphacoronaviruses. In further embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, OC43, NL63, and 229E.

[0107] Binding data are shown in the accompanying figures for the antibodies described below.

[0108] a. Monoclonal antibody COV44-79 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV44-79 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0109] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV44-79 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus may be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment neutralizes a betacoronavirus and an alphacoronavirus. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, OC43, NL63, and 229E.

[0110] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 17. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO:21. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 17 and 21, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0111] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 18, 19 and 20, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 22, 23, and 24, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0112] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 18, 19 and 20, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 22, 23, and 24, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 17, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 17, and V L comprises an amino acid sequence at least 90% identical to SEQ ID NO:21, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:21, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0113] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO:21. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 17 and 21, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0114] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0115] b. Monoclonal antibody COV44-62 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV44-62 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus. In some examples, the antibody or antigen-binding fragment comprises a V-type antibody that specifically binds to the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV44-62 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus may be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment neutralizes a betacoronavirus and an alphacoronavirus. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, OC43, NL63, and 229E.

[0116] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO:9. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 13. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 9 and 13, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0117] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 10, 11 and 12, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 14, 15, and 16, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0118] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 10, 11, and 12, respectively. H, V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 14, 15, and 16 L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 9, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 9, and V L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 13, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0119] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 13. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 9 and 13, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0120] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0121] c. Monoclonal antibody COV89-22 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV89-22 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0122] In some examples, the antibody or antigen-binding fragment comprises a V domain that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV89-22 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus may be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43. In some embodiments, the antibody or antigen-binding fragment neutralizes betacoronaviruses and alphacoronaviruses. In some embodiments, the antibody or antigen-binding fragment specifically binds to a stem helix in the S2 domain of the spike protein.

[0123] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO:1. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO:5. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 1 and 5, respectively. H and V Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0124] In some embodiments, the antibody or antigen-binding fragment comprises a V HCDR1, HCDR2, and HCDR3 sequence shown as SEQ ID NOs: 2, 3, and 4, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 6, 7, and 8, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0125] In some embodiments, the antibody or antigen-binding fragment comprises a V HCDR1, HCDR2, and HCDR3 sequence shown as SEQ ID NOs: 2, 3, and 4, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 6, 7, and 8, respectively L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 1, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 1, and V L comprises an amino acid sequence at least 90% identical to SEQ ID NO:5, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:5, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0126] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO:5. Land specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 1 and 5, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0127] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0128] d. Monoclonal antibody COV30-14 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV30-14 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0129] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV30-14 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus may be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43. In some embodiments, the antibody or antigen-binding fragment neutralizes betacoronaviruses and alphacoronaviruses. In some embodiments, the antibody or antigen-binding fragment specifically binds to a stem helix in the S2 domain of the spike protein.

[0130] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO:25. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO:29. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 25 and 29, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0131] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 26, 27, and 28, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 30, 31, and 32, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0132] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 26, 27, and 28, respectively. H, V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 30, 31, and 32, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 25, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 25, and V L comprises an amino acid sequence at least 90% identical to SEQ ID NO:29, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:29, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0133] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO:29. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 25 and 29, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0134] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0135] e. Monoclonal antibody COV72-37 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV72-37 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0136] In some examples, the antibody or antigen-binding fragment comprises a V sequence comprising the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV72-37 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus may be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43. In some embodiments, the antibody or antigen-binding fragment neutralizes betacoronaviruses and alphacoronaviruses. In some embodiments, the antibody or antigen-binding fragment specifically binds to a stem helix in the S2 domain of the spike protein.

[0137] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 33. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 37. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 33 and 37, respectively. H and V Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0138] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 34, 35, and 36, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 38, 39, and 40, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0139] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 34, 35, and 36, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 38, 39, and 40, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 33, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 33, and V L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 37, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 37, and the antibody or antigen-binding fragment specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside the CDRs. The coronavirus may be SARS-CoV-2.

[0140] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 37. Land specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 33 and 37, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0141] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0142] f. Monoclonal antibody COV91-27 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV91-27 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0143] In some examples, the antibody or antigen-binding fragment comprises a V domain that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV91-27 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, OC43, NL63, and 229E. In some embodiments, the antibody or antigen-binding fragment neutralizes betacoronaviruses and alphacoronaviruses.

[0144] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO:49. Hand specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 53. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 49 and 53, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0145] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 50, 51 and 52, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 54, 55, and 56, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0146] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 50, 51 and 52, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 54, 55, and 56, respectively. L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 49, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 49, and V Lcomprises an amino acid sequence at least 90% identical to SEQ ID NO: 53, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 53, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0147] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 53. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 49 and 53, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0148] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0149] g. Monoclonal antibody COV93-03 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV93-03 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0150] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV93-03 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus may be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43. In some embodiments, the antibody or antigen-binding fragment neutralizes betacoronaviruses and alphacoronaviruses. In some embodiments, the antibody or antigen-binding fragment specifically binds to a stem helix in the S2 domain of the spike protein.

[0151] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO:41. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO:45. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 41 and 45, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0152] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 42, 43 and 44, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 46, 47, and 48, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0153] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 42, 43 and 44, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 46, 47, and 48, respectively. L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 41, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 41, and V L comprises an amino acid sequence at least 90% identical to SEQ ID NO:45, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:45, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0154] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO:45. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 41 and 45, respectively. H and VL and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0155] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0156] h. Monoclonal antibody COV49-51 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV49-51 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0157] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV49-51 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus may be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43. In some embodiments, the antibody or antigen-binding fragment neutralizes betacoronaviruses and alphacoronaviruses. In some embodiments, the antibody or antigen-binding fragment specifically binds to a stem helix in the S2 domain of the spike protein.

[0158] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 57. Hand specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO:61. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 57 and 61, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0159] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 58, 59 and 60, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 62, 63, and 64, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0160] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 58, 59 and 60, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 62, 63, and 64, respectively. L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 57, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 57, and V Lcomprises an amino acid sequence at least 90% identical to SEQ ID NO:61, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:61, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0161] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO:61. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 57 and 61, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0162] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0163] i. Monoclonal antibody COV44-74 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV44-74 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0164] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV44-74 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus may be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43. In some embodiments, the antibody or antigen-binding fragment neutralizes betacoronaviruses and alphacoronaviruses. In some embodiments, the antibody or antigen-binding fragment specifically binds to a stem helix in the S2 domain of the spike protein.

[0165] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 65. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO:69. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 65 and 69, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0166] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 66, 67, and 68, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 70, 71, and 72, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0167] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 66, 67, and 68, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 70, 71, and 72, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 65, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 65, and V L comprises an amino acid sequence at least 90% identical to SEQ ID NO:69, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:69, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0168] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO:69. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 65 and 69, respectively. H and VL and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0169] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0170] j. Monoclonal antibody COV44-56 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV44-56 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0171] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV44-56 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus may be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43. In some embodiments, the antibody or antigen-binding fragment neutralizes betacoronaviruses and alphacoronaviruses. In some embodiments, the antibody or antigen-binding fragment specifically binds to a stem helix in the S2 domain of the spike protein.

[0172] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 73. Hand specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 77. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 73 and 77, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0173] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 74, 75, and 76, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 78, 79, and 80, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0174] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 74, 75, and 76, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 78, 79, and 80, respectively. L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 73, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 73, and V Lcomprises an amino acid sequence at least 90% identical to SEQ ID NO: 77, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 77, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0175] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 77. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 73 and 77, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0176] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0177] k. Monoclonal antibody COV44-26

[0178] In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV44-26 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0179] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV44-26 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and VL and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus may be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43. In some embodiments, the antibody or antigen-binding fragment neutralizes betacoronaviruses and alphacoronaviruses. In some embodiments, the antibody or antigen-binding fragment specifically binds to a stem helix in the S2 domain of the spike protein.

[0180] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 81. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 85. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 81 and 85, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0181] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 82, 83, and 84, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 86, 87, and 88, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0182] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 82, 83, and 84, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 86, 87, and 88, respectively. L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 81, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 81, and V L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 85, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 85, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0183] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 85. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 81 and 85, respectively. H and VL and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0184] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0185] l. Monoclonal antibody COV44-54 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV44-54 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0186] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV44-54 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus may be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43. In some embodiments, the antibody or antigen-binding fragment neutralizes betacoronaviruses and alphacoronaviruses. In some embodiments, the antibody or antigen-binding fragment specifically binds to a stem helix in the S2 domain of the spike protein.

[0187] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 89. Hand specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 93. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 89 and 93, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0188] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 90, 91 and 92, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 94, 95, and 96, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0189] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 90, 91 and 92, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 94, 95, and 96, respectively. L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 89, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 89, and V Lcomprises an amino acid sequence at least 90% identical to SEQ ID NO:93, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:93, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0190] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 93. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 89 and 93, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0191] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0192] m. Monoclonal antibody COV23-01 In some embodiments, the antibody or antigen-binding fragment is based on or derived from a COV23-01 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0193] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV23-01 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0194] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 97. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 101. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 97 and 101, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0195] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 98, 99 and 100, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 102, 103, and 104, respectively. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0196] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 98, 99 and 100, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 102, 103, and 104, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 97, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 97, L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 101, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 101, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0197] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 101. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 97 and 101, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0198] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0199] n. Monoclonal antibody COV49-03 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV49-03 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0200] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV49-03 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0201] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 105. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 109. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 105 and 109, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0202] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 106, 107 and 108, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 110, 111, and 112, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0203] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 106, 107 and 108, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 110, 111, and 112, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 105, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 105, and V Lcomprises an amino acid sequence at least 90% identical to SEQ ID NO: 109, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 109, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0204] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 109. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 105 and 109, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0205] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0206] Monoclonal antibody COV49-04 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV49-04 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0207] In some examples, the antibody or antigen-binding fragment comprises a V molecule comprising the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV49-04 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0208] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 113. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 117. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 113 and 117, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0209] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 114, 115, and 116, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 118, 119, and 120, respectively. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0210] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 114, 115, and 116, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 118, 119, and 120, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 113, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 113, and V L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 117, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 117, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0211] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 117. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 113 and 117, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0212] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0213] p. Monoclonal antibody COV49-05 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV49-05 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0214] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV49-05 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0215] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 121. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 125. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 121 and 125, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0216] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 122, 123, and 124, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 126, 127, and 128, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0217] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 122, 123, and 124, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 126, 127, and 128, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 121, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 121, and V Lcomprises an amino acid sequence at least 90% identical to SEQ ID NO: 125, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 125, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0218] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 125. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 121 and 125, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0219] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0220] q. Monoclonal antibody COV49-06 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV49-06 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0221] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV49-06 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0222] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 129. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 133. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 129 and 133, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0223] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 130, 131 and 132, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 134, 135, and 136, respectively. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0224] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 130, 131 and 132, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 134, 135, and 136, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 129, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 129, and V L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 133, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 133, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0225] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 133. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 129 and 133, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0226] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0227] r. Monoclonal antibody COV49-07 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV49-07 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0228] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV49-07 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0229] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 137. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 141. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 137 and 141, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0230] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 138, 139 and 140, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 142, 143, and 144, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0231] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 138, 139 and 140, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 142, 143, and 144, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 137, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 137, and V Lcomprises an amino acid sequence at least 90% identical to SEQ ID NO: 141, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 141, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0232] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 141. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 137 and 141, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0233] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0234] s. Monoclonal antibody COV49-18 In some embodiments, the antibody or antigen-binding fragment is based on or derived from a COV49-18 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0235] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of a COV49-18 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0236] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 145. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 149. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 145 and 149, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0237] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 146, 147, and 148, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 150, 151, and 152, respectively. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0238] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 146, 147, and 148, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 150, 151, and 152, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 145, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 145, L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 149, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 149, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0239] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 149. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 145 and 149, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0240] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0241] t. Monoclonal antibody COV49-23 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV49-23 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0242] In some examples, the antibody or antigen-binding fragment comprises a V domain that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV49-23 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0243] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 153. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 157. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 153 and 157, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0244] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 154, 155 and 156, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 158, 159, and 160, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0245] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 154, 155 and 156, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 158, 159, and 160, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 153, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 153, and V Lcomprises an amino acid sequence at least 90% identical to SEQ ID NO: 157, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 157, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0246] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 157. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 153 and 157, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0247] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0248] u. Monoclonal antibody COV49-28 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV49-28 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0249] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV49-28 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0250] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 161. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 165. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 161 and 165, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0251] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 162, 163, and 164, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 166, 167, and 168, respectively. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0252] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 162, 163, and 164, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 166, 167, and 168, respectively. L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 161, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 161, L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 165, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 165, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0253] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 165. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 161 and 165, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0254] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0255] v. Monoclonal antibody COV49-30 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV49-30 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0256] In some examples, the antibody or antigen-binding fragment comprises a V domain that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV49-30 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0257] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 169. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 173. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 169 and 173, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0258] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 170, 171 and 172, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 174, 175, and 176, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0259] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 170, 171 and 172, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 174, 175, and 176, respectively. L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 169, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 169, and V Lcomprises an amino acid sequence at least 90% identical to SEQ ID NO: 173, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 173, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0260] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 173. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 169 and 173, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0261] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0262] w. Monoclonal antibody COV49-33 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV49-33 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0263] In some examples, the antibody or antigen-binding fragment comprises a V sequence comprising the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV49-33 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0264] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 177. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 181. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 177 and 181, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0265] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 178, 179, and 180, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 182, 183, and 184, respectively. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0266] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 178, 179, and 180, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 182, 183, and 184, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 177, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 177, L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 181, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 181, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0267] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 181. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 177 and 181, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0268] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0269] x. Monoclonal antibody COV49-42 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV49-42 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0270] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV49-42 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0271] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 185. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 189. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 185 and 189, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0272] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 186, 187, and 188, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 190, 191, and 192, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0273] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 186, 187, and 188, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 190, 191, and 192 L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 185, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 185, L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 189, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 189, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0274] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 189. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 185 and 189, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0275] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0276] y. Monoclonal antibody COV49-47 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV49-47 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0277] In some examples, the antibody or antigen-binding fragment comprises a V sequence comprising the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV49-47 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0278] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 193. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 197. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 193 and 197, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0279] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 194, 195 and 196, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 198, 199, and 200, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0280] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 194, 195 and 196, respectively. H, V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 198, 199, and 200, respectively. L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 193, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 193, and V L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 197, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 197, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0281] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 197. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 193 and 197, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0282] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0283] z. Monoclonal antibody COV49-54 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV49-54 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0284] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV49-54 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0285] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO:201. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 205. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 201 and 205, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0286] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 202, 203, and 204, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 206, 207, and 208, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0287] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 202, 203, and 204, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 206, 207, and 208, respectively. L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 201, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 201, L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 205, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 205, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0288] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 205. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 201 and 205, respectively.H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0289] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0290] aa. Monoclonal antibody COV57-01 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV57-01 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0291] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV57-01 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0292] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 209. Hand specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 213. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 209 and 213, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0293] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 210, 211 and 212, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 214, 215, and 216, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0294] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 210, 211 and 212, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 214, 215, and 216, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 209, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 209, Lcomprises an amino acid sequence at least 90% identical to SEQ ID NO: 213, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 213, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0295] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 213. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 209 and 213, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0296] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0297] bb. Monoclonal antibody COV57-03 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV57-03 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0298] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV57-03 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0299] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 217. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 221. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 217 and 221, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0300] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 218, 219, and 220, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 222, 223, and 224, respectively. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0301] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 218, 219, and 220, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 222, 223, and 224, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 217, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 217, and V L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 221, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 221, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0302] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 221. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 217 and 221, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0303] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0304] cc. Monoclonal antibody COV57-04 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV57-04 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0305] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV57-04 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0306] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 225. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 229. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 225 and 229, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0307] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 226, 227, and 228, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 230, 231, and 232, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0308] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 226, 227, and 228, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 230, 231, and 232, respectively. L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 225, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 225, Lcomprises an amino acid sequence at least 90% identical to SEQ ID NO: 229, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 229, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0309] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 229. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 225 and 229, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0310] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0311] dd. Monoclonal antibody COV57-05 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV57-05 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0312] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV57-05 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0313] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 233. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 237. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 233 and 237, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0314] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 234, 235, and 236, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 238, 239, and 240, respectively. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0315] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 234, 235, and 236, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 238, 239, and 240, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 233, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 233, and V L comprises an amino acid sequence at least 90% identical to SEQ ID NO:237, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:237, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0316] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 237. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 233 and 237, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0317] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0318] ee. Monoclonal antibody COV57-13 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV57-13 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0319] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV57-13 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0320] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO:241. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 245. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 241 and 245, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0321] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 242, 243, and 244, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 246, 247, and 248, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0322] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 242, 243, and 244, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 246, 247, and 248 L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 241, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 241, L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 245, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 245, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0323] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 245. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 241 and 245, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0324] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0325] ff. Monoclonal antibody COV57-19 In some embodiments, the antibody or antigen-binding fragment is based on or derived from a COV57-19 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0326] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of a COV57-19 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0327] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO:249. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 253. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 249 and 253, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0328] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 250, 251 and 252, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 254, 255, and 256, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0329] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 250, 251 and 252, respectively. H, V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 254, 255, and 256, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 249, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 249, and V L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 253, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 253, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0330] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 253. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 249 and 253, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0331] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0332] gg. Monoclonal antibody COV57-34 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV57-34 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0333] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV57-34 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0334] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 257. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 261. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 257 and 261, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0335] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 258, 259, and 260, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 262, 263, and 264, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0336] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 258, 259, and 260, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 262, 263, and 264, respectively. L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 257, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 257, and V L comprises an amino acid sequence at least 90% identical to SEQ ID NO:261, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:261, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0337] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 261. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 257 and 261, respectively.H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0338] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0339] hh. Monoclonal antibody COV57-38 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV57-38 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0340] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV57-38 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0341] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 265. Hand specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 269. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 265 and 269, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0342] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 266, 267, and 268, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 270, 271, and 272, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0343] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 266, 267, and 268, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 270, 271, and 272, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 265, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 265, Lcomprises an amino acid sequence at least 90% identical to SEQ ID NO: 269, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 269, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0344] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 269. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 265 and 269, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0345] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0346] ii. Monoclonal antibody COV57-45 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV57-45 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0347] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV57-45 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0348] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 273. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 277. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 273 and 277, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0349] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 274, 275, and 276, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 278, 279, and 280, respectively. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0350] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 274, 275, and 276, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 278, 279, and 280, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 273, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 273, and V L comprises an amino acid sequence at least 90% identical to SEQ ID NO:277, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:277, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0351] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 277. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 273 and 277, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0352] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0353] jj. Monoclonal antibody COV77-02 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV77-02 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0354] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV77-02 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0355] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO:281. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 285. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 281 and 285, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0356] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 282, 283, and 284, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 286, 287, and 288, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0357] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 282, 283, and 284, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 286, 287, and 288, respectively. L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 281, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 281, Lcomprises an amino acid sequence at least 90% identical to SEQ ID NO:285, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:285, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0358] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 285. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 281 and 285, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0359] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0360] kk. Monoclonal antibody COV77-04 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV77-04 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0361] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV77-04 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, OC43, NL63, and 229E.

[0362] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO:289. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 293. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 289 and 293, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0363] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 290, 291, and 292, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 294, 295, and 296, respectively. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0364] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 290, 291 and 292, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 294, 295, and 296, respectively. L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 289, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 289, and V L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 293, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 293, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0365] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 293. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 289 and 293, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0366] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0367] ll. Monoclonal antibody COV77-05 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV77-05 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0368] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV77-05 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0369] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO:297. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 301. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 297 and 301, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0370] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 298, 299 and 300, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 302, 303, and 304, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0371] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2 and HCDR3 set forth as SEQ ID NOs: 298, 299 and 300, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 302, 303, and 304, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 297, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 297, Lcomprises an amino acid sequence at least 90% identical to SEQ ID NO: 301, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 301, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0372] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 301. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 297 and 301, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0373] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0374] mm. Monoclonal antibody COV77-09 In some embodiments, the antibody or antigen-binding fragment is based on or derived from a COV77-09 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0375] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of a COV77-09 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus may be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43. In some embodiments, the antibody or antigen-binding fragment specifically binds to a stem helix in the S2 domain of the spike protein.

[0376] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 305. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 309. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 305 and 309, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0377] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 306, 307, and 308, respectively. Hand / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 310, 311, and 312, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0378] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 306, 307, and 308, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 310, 311, and 312, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 305, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 305, L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 309, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 309, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0379] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 309. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 305 and 309, respectively. H and V Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0380] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0381] nn. Monoclonal antibody COV77-14 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV77-14 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0382] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV77-14 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0383] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 313. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 317.L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 313 and 317, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0384] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 314, 315, and 316, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 318, 319, and 320, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0385] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 314, 315, and 316, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 318, 319, and 320, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 313, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 313, and V Lcomprises an amino acid sequence at least 90% identical to SEQ ID NO: 317, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 317, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0386] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 317. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 313 and 317, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0387] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0388] oo. Monoclonal antibody COV77-35 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV77-35 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0389] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV77-35 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0390] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 321. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 325. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 321 and 325, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0391] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 322, 323, and 324, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 326, 327, and 328, respectively. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0392] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 322, 323, and 324, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 326, 327, and 328, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 321, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 321, L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 325, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 325, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0393] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 325. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 321 and 325, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0394] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0395] pp. Monoclonal antibody COV77-39 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV77-39 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0396] In some examples, the antibody or antigen-binding fragment comprises a V sequence comprising the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV77-39 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, OC43, NL63, and 229E.

[0397] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 329. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 333. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 329 and 333, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0398] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 330, 331, and 332, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 334, 335, and 336, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0399] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 330, 331, and 332, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 334, 335, and 336, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 329, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 329, Lcomprises an amino acid sequence at least 90% identical to SEQ ID NO: 333, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 333, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0400] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 333. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 329 and 333, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0401] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0402] qq. Monoclonal antibody COV77-42 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV77-42 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0403] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV77-42 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0404] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 337. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 341. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 337 and 341, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0405] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 338, 339, and 340, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 342, 343, and 344, respectively. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0406] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 338, 339, and 340, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 342, 343, and 344, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 337, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 337, and V L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 341, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 341, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0407] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 341. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 337 and 341, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0408] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0409] rr. Monoclonal antibody COV77-43 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV77-43 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0410] In some examples, the antibody or antigen-binding fragment comprises a V domain that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV77-43 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0411] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 345. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 349. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 345 and 349, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0412] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 346, 347, and 348, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 350, 351, and 352, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0413] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 346, 347, and 348, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 350, 351, and 352, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 345, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 345, Lcomprises an amino acid sequence at least 90% identical to SEQ ID NO: 349, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 349, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0414] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 349. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 345 and 349, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0415] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0416] ss. Monoclonal antibody COV77-46 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV77-46 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0417] In some examples, the antibody or antigen-binding fragment comprises a V domain that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV77-46 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0418] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 353. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 357. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 353 and 357, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0419] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 354, 355, and 356, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 358, 359, and 360, respectively. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0420] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 354, 355, and 356, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 358, 359, and 360, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 353, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 353, and V L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 357, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 357, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 357. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 353 and 357, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0421] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0422] tt. Monoclonal antibody COV77-76 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV77-76 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0423] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV77-76 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0424] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 361. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 365. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 361 and 365, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0425] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 362, 363, and 364, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 366, 367, and 368, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0426] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 362, 363, and 364, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 366, 367, and 368, respectively. L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 361, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 361, Lcomprises an amino acid sequence at least 90% identical to SEQ ID NO: 365, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 365, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0427] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 365. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 361 and 365, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0428] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0429] uu. Monoclonal antibody COV93-04 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV93-04 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0430] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV93-04 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0431] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 369. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 373. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 369 and 373, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0432] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 370, 371, and 372, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 374, 375, and 376, respectively. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0433] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 370, 371, and 372, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 374, 375, and 376, respectively. L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 369, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 369, L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 373, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 373, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0434] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 373. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 369 and 373, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0435] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0436] vv. Monoclonal antibody COV93-08 In some embodiments, the antibody or antigen-binding fragment is based on or derived from a COV93-08 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0437] In some examples, the antibody or antigen-binding fragment comprises a V domain that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV93-08 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0438] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 377. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In further embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 381. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 377 and 381, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0439] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 378, 379, and 380, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 382, ​​383, and 384, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0440] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 378, 379, and 380, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 382, ​​383, and 384, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 377, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 377, Lcomprises an amino acid sequence at least 90% identical to SEQ ID NO: 381, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 381, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0441] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 381. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 377 and 381, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0442] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0443] www.Monoclonal antibody COV93-17 In some embodiments, the antibody or antigen-binding fragment is based on or derived from a COV93-17 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0444] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV93-17 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0445] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 385. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 389. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 385 and 389, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0446] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 386, 387, and 388, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 390, 391, and 392, respectively. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0447] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 386, 387, and 388, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 390, 391, and 392, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 385, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 385, L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 389, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 389, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0448] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 389. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 385 and 389, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0449] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0450] xx. Monoclonal antibody COV93-18 In some embodiments, the antibody or antigen-binding fragment is based on or derived from a COV93-18 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0451] In some examples, the antibody or antigen-binding fragment comprises a V that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV93-18 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0452] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 393. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO: 397. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 393 and 397, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0453] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 394, 395, and 396, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 398, 399, and 400, respectively. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0454] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 394, 395, and 396, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 398, 399, and 400, respectively; L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 393, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 393, and V Lcomprises an amino acid sequence at least 90% identical to SEQ ID NO: 397, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 397, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside the CDRs. The coronavirus may be SARS-CoV-2.

[0455] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO: 397. L and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 393 and 397, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0456] In some embodiments, the disclosed antibodies inhibit viral entry and / or replication.

[0457] Monoclonal antibody COV93-23 In some embodiments, the antibody or antigen-binding fragment is based on or derived from the COV93-23 antibody, specifically binds to the coronavirus spike protein, and neutralizes the coronavirus.

[0458] In some examples, the antibody or antigen-binding fragment comprises a V domain that contains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the COV93-23 antibody, respectively (e.g., according to IMGT, Kabat, or Chothia). H and V Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus. The coronavirus can be SARS-CoV-2. In some embodiments, the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

[0459] In some embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO:401. H and specifically binds to coronavirus spikes and neutralizes coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence set forth as SEQ ID NO:405. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In additional embodiments, the antibody or antigen-binding fragment comprises a V that comprises an amino acid sequence that is at least 90% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequences set forth as SEQ ID NOs: 401 and 405, respectively. H and V L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0460] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 402, 403, and 404, respectively. H and / or V comprising LCDR1, LCDR2, and LCDR3 set forth as SEQ ID NOs: 406, 407, and 408, respectively. Land specifically binds to a coronavirus spike protein and neutralizes the coronavirus, which may be SARS-CoV-2.

[0461] In some embodiments, the antibody or antigen-binding fragment comprises a V sequence comprising HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 402, 403, and 404, respectively. H , V comprising LCDR1, LCDR2, and LCDR3 shown as SEQ ID NOs: 406, 407, and 408, respectively. L Including V H comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 401, such as 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 401, L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 405, such as 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 405, and the antibody or antigen-binding fragment specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In this embodiment, variations due to sequence identity fall outside of the CDRs. The coronavirus may be SARS-CoV-2.

[0462] In some embodiments, the antibody or antigen-binding fragment comprises a V H and specifically binds to the coronavirus spike protein and neutralizes the coronavirus. In a further embodiment, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequence set forth as SEQ ID NO:405. L and specifically binds to a coronavirus spike protein and neutralizes the coronavirus. In some embodiments, the antibody or antigen-binding fragment comprises a V comprising the amino acid sequences set forth as SEQ ID NOs: 40...

Claims

1. Heavy chain variable (V Ｈ ) region and the light chain variable region (V Ｌ ) where a) SEQ ID NOs: 17 and 21 (COV44-79), respectively; b) SEQ ID NOs: 9 and 13 (COV44-62), respectively; c) SEQ ID NOs: 1 and 5 (COV89-22), respectively; d) SEQ ID NOs: 25 and 29 (COV30-14), respectively; e) SEQ ID NOs: 33 and 37 (COV72-37), respectively; f) SEQ ID NOs: 49 and 53 (COV91-27), respectively; g) SEQ ID NOs: 41 and 45 (COV93-03), respectively; h) SEQ ID NOs: 57 and 61 (COV49-51), respectively; i) SEQ ID NOs: 65 and 69 (COV44-74), respectively; j) SEQ ID NOs: 73 and 77 (COV44-56), respectively; k) SEQ ID NOs: 81 and 85 (COV44-26), respectively; l) SEQ ID NOs: 89 and 93 (COV44-54), respectively; m) SEQ ID NOs: 97 and 101 (COV23-01), respectively; n) SEQ ID NOs: 105 and 109 (COV49-03), respectively; o) SEQ ID NOs: 113 and 117 (COV49-04), respectively; p) SEQ ID NOs: 121 and 125 (COV49-05), respectively; q) SEQ ID NOs: 129 and 133 (COV49-06), respectively; r) SEQ ID NOs: 137 and 141 (COV49-07), respectively; s) SEQ ID NOs: 145 and 149 (COV49-18), respectively; t) SEQ ID NOs: 153 and 157 (COV49-23), respectively; u) SEQ ID NOs: 161 and 165 (COV49-28), respectively; v) SEQ ID NOs: 169 and 173 (COV49-30), respectively; w) SEQ ID NOs: 177 and 181 (COV49-33), respectively; x) SEQ ID NOs: 185 and 189 (COV49-42), respectively; y) SEQ ID NOs: 193 and 197 (COV49-47), respectively; z) SEQ ID NOs: 201 and 205 (COV49-54), respectively; aa) SEQ ID NOs: 209 and 213 (COV57-01), respectively; bb) SEQ ID NOs: 217 and 221 (COV57-03), respectively; cc) SEQ ID NOs: 225 and 229 (COV57-04), respectively; dd) SEQ ID NOs: 233 and 237 (COV57-05), respectively; ee) SEQ ID NOs: 241 and 245 (COV57-13), respectively; ff) SEQ ID NOs: 249 and 253 (COV57-19), respectively; gg) SEQ ID NOs: 257 and 261 (COV57-34), respectively; hh) SEQ ID NOs: 265 and 269 (COV57-38), respectively; ii) SEQ ID NOs: 273 and 277 (COV57-45), respectively; jj) SEQ ID NOs: 281 and 285 (COV77-02), respectively; kk) SEQ ID NOs: 289 and 293 (COV77-04), respectively; ll) SEQ ID NOs: 297 and 301 (COV77-05), respectively; mm) SEQ ID NOs: 305 and 309 (COV77-09), respectively; nn) SEQ ID NOs: 313 and 317 (COV77-14), respectively; oo) SEQ ID NOs: 321 and 325 (COV77-35), respectively; pp) SEQ ID NOs: 329 and 333 (COV77-39), respectively; qq) SEQ ID NOs: 337 and 341 (COV77-42), respectively; rr) SEQ ID NOs: 345 and 349 (COV77-43), respectively; ss) SEQ ID NOs: 353 and 357 (COV77-46), respectively; tt) SEQ ID NOs: 361 and 365 (COV77-76), respectively; uu) SEQ ID NOs: 369 and 373 (COV93-04), respectively; vv) SEQ ID NOs: 377 and 381 (COV93-08), respectively; ww) SEQ ID NOs: 385 and 389 (COV93-17), respectively; xx) SEQ ID NOs: 393 and 397 (COV93-18), respectively; yy) SEQ ID NOs: 401 and 405 (COV93-23), respectively; zz) SEQ ID NOs: 409 and 413 (COV78-36), respectively; aaa) SEQ ID NOs: 417 and 421 (COV93-38), respectively; bbb) SEQ ID NOs: 425 and 429 (COV93-60), respectively; ccc) SEQ ID NOs: 433 and 437 (COV93-61), respectively; ddd) SEQ ID NOs: 441 and 445 (COV89-03), respectively; eee) SEQ ID NOs: 449 and 453 (COV89-28), respectively; fff) SEQ ID NOs: 457 and 461 (COV30-35), respectively; ggg) SEQ ID NOs: 465 and 469 (COV30-80), respectively; hhh) SEQ ID NOs: 473 and 477 (COV44-25), respectively; or iii) SEQ ID NOs: 481 and 485 (COV44-37), respectively The V is represented as any one of Ｈ and V Ｌ V comprising heavy chain complementarity determining regions (HCDR) 1, HCDR2, and HCDR3, and light chain complementarity determining regions (LCDR) 1, LCDR2, and LCDR3 of Ｈ and V Ｌ 1. An isolated monoclonal antibody or antigen-binding fragment thereof comprising: The monoclonal antibody is an antibody or antigen-binding fragment that specifically binds to the coronavirus spike protein.

2. the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2, and the LCDR3 are each a) SEQ ID NOs: 18, 19, 20, 22, 23 (AAS), and 24; b) SEQ ID NOs: 10, 11, 12, 14, 15 (EVT), and 16; c) SEQ ID NOs: 2, 3, 4, 6, 7 (DAS), and 8; d) SEQ ID NOs: 26, 27, 28, 30, 31 (GES), and 32; e) SEQ ID NOs: 34, 35, 36, 38, 39 (GAS), and 40; f) SEQ ID NOs: 50, 51, 52, 54, 55 (DAS), and 56; g) SEQ ID NOs: 42, 43, 44, 46, 47 (GAS), and 48; h) SEQ ID NOs: 58, 59, 60, 62, 63 (GAS), and 64; i) SEQ ID NOs: 66, 67, 68, 70, 71 (AAS), and 72; j) SEQ ID NOs: 74, 75, 76, 78, 79 (LGS), and 80; k) SEQ ID NOs: 82, 83, 84, 86, 87 (AAS), and 88; l) SEQ ID NOs: 90, 91, 92, 94, 95 (AAS), and 96; m) SEQ ID NOs: 98, 99, 100, 102, 103 (DAS), and 104; n) SEQ ID NOs: 106, 107, 108, 110, 111 (KVS), and 112; o) SEQ ID NOs: 114, 115, 116, 118, 119 (RVS), and 120; p) SEQ ID NOs: 122, 123, 124, 126, 127 (QVS), and 128; q) SEQ ID NOs: 130, 131, 132, 134, 135 (KVS), and 136; r) SEQ ID NOs: 138, 139, 140, 142, 143 (KVS), and 144; s) SEQ ID NOs: 146, 147, 148, 150, 151 (KVS), and 152; t) SEQ ID NOs: 154, 155, 156, 158, 159 (QVS), and 160; u) SEQ ID NOs: 162, 163, 164, 166, 167 (QVS), and 168; v) SEQ ID NOs: 170, 171, 172, 174, 175 (KVS), and 176; w) SEQ ID NOs: 178, 179, 180, 182, 183 (QVS), and 184; x) SEQ ID NOs: 186, 187, 188, 190, 191 (AAS), and 192; y) SEQ ID NOs: 194, 195, 196, 198, 199 (QVS), and 200; z) SEQ ID NOs: 202, 203, 204, 206, 207 (AAS), and 208; aa) SEQ ID NOs: 210, 211, 212, 214, 215 (TAS), and 216; bb) SEQ ID NOs: 218, 219, 220, 222, 223 (WAS), and 224; cc) SEQ ID NOs: 226, 227, 228, 230, 231 (WAS), and 232; dd) SEQ ID NOs: 234, 235, 236, 238, 239 (DAS), and 240; ee) SEQ ID NOs: 242, 243, 244, 246, 247 (WAS), and 248; ff) SEQ ID NOs: 250, 251, 252, 254, 25(DAS)5, and 256; gg) SEQ ID NOs: 258, 259, 260, 262, 263 (WAS), and 264; hh) SEQ ID NOs: 266, 267, 268, 270, 271 (RDN), and 272; ii) SEQ ID NOs: 274, 275, 276, 278, 279 (WAS), and 280; jj) SEQ ID NOs: 282, 283, 284, 286, 287 (LGS), and 288; kk) SEQ ID NOs: 290, 291, 292, 294, 295 (KDS), and 296; ll) SEQ ID NOs: 298, 299, 300, 302, 303 (GAS), and 304; mm) SEQ ID NOs: 306, 307, 308, 310, 311 (WAS), and 312; nn) SEQ ID NOs: 314, 315, 316, 318, 319 (GAS), and 320; oo) SEQ ID NOs: 322, 323, 324, 326, 327 (GAS), and 328; pp) SEQ ID NOs: 330, 331, 332, 334, 335 (KDR), and 336; qq) SEQ ID NOs: 338, 339, 340, 342, 343 (GAS), and 344; rr) SEQ ID NOs: 346, 347, 348, 350, 351 (LGS), and 352; ss) SEQ ID NOs: 354, 355, 356, 358, 359 (GAS), and 360; tt) SEQ ID NOs: 362, 363, 364, 366, 367 (WAS), and 368; uu) SEQ ID NOs: 370, 371, 372, 374, 375 (WAS), and 376; vv) SEQ ID NOs: 378, 379, 380, 382, ​​383 (KAS), and 384; ww) SEQ ID NOs: 386, 387, 388, 390, 391 (RAS), and 392; xx) SEQ ID NOs: 394, 395, 396, 398, 399 (WAS) and 400; yy) SEQ ID NOs: 402, 403, 404, 406, 407 (WAS), and 408; zz) SEQ ID NOs: 410, 411, 412, 414, 415 (EVS), and 416; aaa) SEQ ID NOs: 418, 419, 420, 422, 423 (KAS), and 424; bbb) SEQ ID NOs: 426, 427, 428, 430, 431 (WAS), and 432; ccc) SEQ ID NOs: 434, 435, 436, 438, 439 (EVT), and 440; ddd) SEQ ID NOs: 442, 443, 444, 446, 447 (WAS), and 448; eee) SEQ ID NOs: 450, 451, 452, 454, 455 (ATS), and 456; fff) SEQ ID NOs: 458, 459, 460, 462, 463 (GAS), and 464; ggg) SEQ ID NOs: 466, 467, 468, 470, 471 (WAS), and 472; hhh) SEQ ID NOs: 474, 475, 476, 478, 479 (WAS), and 480; or iii) The antibody or antigen-binding fragment of claim 1, comprising the amino acid sequence set forth as SEQ ID NOs: 482, 483, 484, 486, 487 (LGS), and 488.

3. The V Ｈ and the V Ｌ However, respectively, a) SEQ ID NOs: 17 and 21; b) SEQ ID NOs: 9 and 13; c) SEQ ID NOs: 1 and 5; d) SEQ ID NOs: 25 and 29; e) SEQ ID NOs: 33 and 37; f) SEQ ID NOs: 49 and 53; g) SEQ ID NOs: 41 and 45; h) SEQ ID NOs: 57 and 61; i) SEQ ID NOs: 65 and 69; j) SEQ ID NOs: 73 and 77; k) SEQ ID NOs: 81 and 85; l) SEQ ID NOs: 89 and 93; m) SEQ ID NOs: 97 and 101; n) SEQ ID NOs: 105 and 109; o) SEQ ID NOs: 113 and 117; p) SEQ ID NOs: 121 and 125; q) SEQ ID NOs: 129 and 133; r) SEQ ID NOs: 137 and 141; s) SEQ ID NOs: 145 and 149; t) SEQ ID NOs: 153 and 157; u) SEQ ID NOs: 161 and 165; v) SEQ ID NOs: 169 and 173; w) SEQ ID NOs: 177 and 181; x) SEQ ID NOs: 185 and 189; y) SEQ ID NOs: 193 and 197; z) SEQ ID NOs: 201 and 205; aa) SEQ ID NOs: 209 and 213; bb) SEQ ID NOs: 217 and 221; cc) SEQ ID NOs: 225 and 229; dd) SEQ ID NOs: 233 and 237; ee) SEQ ID NOs: 241 and 245; ff) SEQ ID NOs: 249 and 253; gg) SEQ ID NOs: 257 and 261; hh) SEQ ID NOs: 265 and 269; ii) SEQ ID NOs: 273 and 277; jj) SEQ ID NOs: 281 and 285; kk) SEQ ID NOs: 289 and 293; ll) SEQ ID NOs: 297 and 301; mm) SEQ ID NOs: 305 and 309; nn) SEQ ID NOs: 313 and 317; oo) SEQ ID NOs: 321 and 325; pp) SEQ ID NOs: 329 and 333; qq) SEQ ID NOs: 337 and 341; rr) SEQ ID NOs: 345 and 349; ss) SEQ ID NOs: 353 and 357; tt) SEQ ID NOs: 361 and 365; uu) SEQ ID NOs: 369 and 373; vv) SEQ ID NOs: 377 and 381; ww) SEQ ID NOs: 385 and 389; xx) SEQ ID NOs: 393 and 397; yy) SEQ ID NOs: 401 and 405; zz) SEQ ID NOs: 409 and 413; aaa) SEQ ID NOs: 417 and 421; bbb) SEQ ID NOs: 425 and 429; ccc) SEQ ID NOs: 433 and 437; ddd) SEQ ID NOs: 441 and 445; eee) SEQ ID NOs: 449 and 453; fff) SEQ ID NOs: 457 and 461; ggg) SEQ ID NOs: 465 and 469; hhh) SEQ ID NOs: 473 and 477; or iii) SEQ ID NOs: 481 and 485 3. The antibody or antigen-binding fragment of claim 1 or claim 2, comprising an amino acid sequence that is at least 90% identical to the amino acid sequence shown as:

4. 3. The antibody or antigen-binding fragment of claim 1 or claim 2, comprising a human framework region.

5. The V Ｈ and the V Ｌ However, respectively, a) SEQ ID NOs: 17 and 21; b) SEQ ID NOs: 9 and 13; c) SEQ ID NOs: 1 and 5; d) SEQ ID NOs: 25 and 29; e) SEQ ID NOs: 33 and 37; f) SEQ ID NOs: 49 and 53; g) SEQ ID NOs: 41 and 45; h) SEQ ID NOs: 57 and 61; i) SEQ ID NOs: 65 and 69; j) SEQ ID NOs: 73 and 77; k) SEQ ID NOs: 81 and 85; l) SEQ ID NOs: 89 and 93; m) SEQ ID NOs: 97 and 101; n) SEQ ID NOs: 105 and 109; o) SEQ ID NOs: 113 and 117; p) SEQ ID NOs: 121 and 125; q) SEQ ID NOs: 129 and 133; r) SEQ ID NOs: 137 and 141; s) SEQ ID NOs: 145 and 149; t) SEQ ID NOs: 153 and 157; u) SEQ ID NOs: 161 and 165; v) SEQ ID NOs: 169 and 173; w) SEQ ID NOs: 177 and 181; x) SEQ ID NOs: 185 and 189; y) SEQ ID NOs: 193 and 197; z) SEQ ID NOs: 201 and 205; aa) SEQ ID NOs: 209 and 213; bb) SEQ ID NOs: 217 and 221; cc) SEQ ID NOs: 225 and 229; dd) SEQ ID NOs: 233 and 237; ee) SEQ ID NOs: 241 and 245; ff) SEQ ID NOs: 249 and 253; gg) SEQ ID NOs: 257 and 261; hh) SEQ ID NOs: 265 and 269; ii) SEQ ID NOs: 273 and 277; jj) SEQ ID NOs: 281 and 285; kk) SEQ ID NOs: 289 and 293; ll) SEQ ID NOs: 297 and 301; mm) SEQ ID NOs: 305 and 309; nn) SEQ ID NOs: 313 and 317; oo) SEQ ID NOs: 321 and 325; pp) SEQ ID NOs: 329 and 333; qq) SEQ ID NOs: 337 and 341; rr) SEQ ID NOs: 345 and 349; ss) SEQ ID NOs: 353 and 357; tt) SEQ ID NOs: 361 and 365; uu) SEQ ID NOs: 369 and 373; vv) SEQ ID NOs: 377 and 381; ww) SEQ ID NOs: 385 and 389; xx) SEQ ID NOs: 393 and 397; yy) SEQ ID NOs: 401 and 405; zz) SEQ ID NOs: 409 and 413; aaa) SEQ ID NOs: 417 and 421; bbb) SEQ ID NOs: 425 and 429; ccc) SEQ ID NOs: 433 and 437; ddd) SEQ ID NOs: 441 and 445; eee) SEQ ID NOs: 449 and 453; fff) SEQ ID NOs: 457 and 461; ggg) SEQ ID NOs: 465 and 469; hhh) SEQ ID NOs: 473 and 477; or iii) SEQ ID NOs: 481 and 485 3. The antibody or antigen-binding fragment of claim 1 or claim 2, comprising the amino acid sequence shown as:

6. 3. The antibody of claim 1 or claim 2, comprising a human constant domain.

7. The antibody of claim 1 or claim 2, which is a human antibody.

8. The antibody of claim 1 or claim 2, which is an IgG.

9. 3. The antibody of claim 1 or claim 2, comprising a recombinant constant domain comprising a modification that increases the half-life of the antibody.

10. The antibody of claim 9, wherein the modification increases binding to a neonatal Fc receptor.

11. 3. The antibody or antigen-binding fragment of claim 1 or claim 2, wherein the antibody specifically binds to the N-terminal domain of the coronavirus spike protein.

12. 3. The antibody or antigen-binding fragment of claim 1 or claim 2, wherein the antibody specifically binds to the S domain of the coronavirus spike protein.

13. The antibody or antigen-binding fragment of claim 1 or claim 2, wherein the antibody neutralizes SARS-CoV-2.

14. An antigen-binding fragment according to claim 1 or claim 2.

15. The antigen-binding fragment may be an Fv, Fab, or F(ab') ２ , scFv or scFv ２ The antigen-binding fragment of claim 14, which is a fragment.

16. The antibody or antigen-binding fragment of claim 1 or claim 2, wherein the antibody or antigen-binding fragment specifically binds to spike proteins from at least three betacoronaviruses selected from the group consisting of SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, and OC43.

17. The antibody or antigen-binding fragment of claim 1 or 2, wherein the antibody or antigen-binding fragment specifically binds to spike proteins from SARS-CoV-2, SARS-CoV, MERS-CoV, HKU1, OC43, NL63, and 229E.

18. The antibody or antigen-binding fragment of claim 1 or claim 2, wherein the antibody or antigen-binding fragment specifically binds to the stem-helix of the S2 domain of the spike protein.

19. 3. The antibody or antigen-binding fragment of claim 1 or claim 2 conjugated to a detectable marker.

20. A bispecific antibody comprising the antibody or antigen-binding fragment of claim 1 or claim 2.

21. The antibody or antigen-binding fragment of claim 1 or claim 2, or the V of said antibody Ｈ Or V Ｌ An isolated nucleic acid molecule encoding

22. The V Ｈ or V Ｌ 22. The nucleic acid molecule of claim 21, which is a cDNA sequence encoding

23. 22. The nucleic acid molecule of claim 21 operably linked to a promoter.

24. A vector comprising the nucleic acid molecule of claim 21.

25. A host cell comprising the nucleic acid molecule of claim 21.

26. A pharmaceutical composition for use in inhibiting coronavirus infection, comprising an effective amount of the antibody or antigen-binding fragment of claim 1 or claim 2, a bispecific antibody comprising said antibody or antigen-binding fragment, a nucleic acid molecule encoding said antibody or antigen-binding fragment, or a vector comprising said nucleic acid molecule; and a pharmaceutically acceptable carrier.

27. 1. A method for producing an antibody or antigen-binding fragment that specifically binds to a coronavirus spike protein, comprising: expressing in a host cell one or more nucleic acid molecules encoding the antibody or antigen-binding fragment of claim 1 or claim 2; and purifying the antibody or antigen-binding fragment.

28. 1. A method for detecting the presence of coronavirus in a biological sample from a subject, comprising: contacting the biological sample with an effective amount of the antibody or antigen-binding fragment of claim 1 or claim 2 under conditions sufficient to form an immune complex; detecting the presence of the immune complex in the biological sample, wherein the presence of the immune complex in the biological sample indicates the presence of the coronavirus in the sample.

29. 29. The method of claim 28, wherein said detecting the presence of said immune complex in said biological sample indicates that said subject has a SARS-CoV-2, SARS-CoV, MERS-CoV, OC43, NL63, 229E, or HKU1 infection.

30. 29. The method of claim 28, wherein said detecting the presence of said immune complex in said biological sample indicates that said subject has a SARS-CoV-2 infection.

31. A composition comprising the antibody or antigen-binding fragment thereof described in claim 1 or claim 2, a composition comprising a nucleic acid molecule encoding the antibody or antigen-binding fragment, a composition comprising a vector comprising the nucleic acid molecule, or a pharmaceutical composition comprising the antibody, antigen-binding fragment, nucleic acid molecule, or vector and a pharmaceutically acceptable carrier, for inhibiting coronavirus infection in a subject, wherein the subject has or is at risk of having a coronavirus infection.

32. 32. The composition or pharmaceutical composition of claim 31, wherein the coronavirus is SARS-CoV-2, SARS-CoV, MERS-CoV, OC43, NL63, 229E, or HKU1.

33. 32. The composition or pharmaceutical composition of claim 31, wherein the coronavirus is SARS-CoV-2.

34. A composition comprising the antibody or antigen-binding fragment thereof described in claim 1 or claim 2, a composition comprising a nucleic acid molecule encoding the antibody or antigen-binding fragment, a composition comprising a vector comprising the nucleic acid molecule, or a pharmaceutical composition comprising the antibody, antigen-binding fragment, nucleic acid molecule, or vector and a pharmaceutically acceptable carrier, for inhibiting coronavirus infection in a subject or detecting the presence of coronavirus in a biological sample.

35. 35. The composition or pharmaceutical composition of claim 34, wherein the coronavirus is SARS-CoV-2, SARS-CoV, MERS-CoV, OC43, NL63, 229E, or HKU1.

36. 35. The composition or pharmaceutical composition of claim 34, wherein the coronavirus is SARS-CoV-2.

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