Antibodies against covid-19 and other human coronaviruses

Abstract

The present invention relates to monoclonal antibodies or antigen-binding portion thereof that have a potent neutralizing activity against Coronavirus, in particular against at least one virus selected from SARS-CoV-2, SARS-CoV-1 and variants thereof. The invention relates also to the use of such monoclonal antibodies or antigen-binding portion thereof in therapy, prophylaxis, and diagnosis of Coronavirus, in particular SARS-CoV-2 and / or SARS-CoV-1 dependent diseases.

Description

ANTIBODIES AGAINST COVID-19 AND OTHER HUMAN CORONAVIRUSESDESCRIPTIONTechnical field of the inventionThe present invention relates to monoclonal antibodies or antigen-binding portion thereof that have a potent neutralizing activity against Coronavirus, in particular against SARS- CoV-2 and SARS-CoV-1. The invention relates also to the use of such monoclonal antibodies or antigen-binding portion thereof in therapy, prophylaxis, and diagnosis of Coronavirus dependent diseases.State of the artHuman monoclonal antibodies (mAbs) are an industrially mature technology with more than 50 products already approved in the field of cancer, inflammation and autoimmunity. The well-established safety profile and the large experience for their development make mAbs ideal candidates for rapid development especially in epidemic and pandemic settings. So far mAbs have rarely been used in the field of infectious diseases, mostly because the large quantities needed for therapy made them not cost effective. However, in recent years, the incredible technological progress in isolating and screening memory B cells allowed identification of highly potent neutralizing mAbs and further improvement of their potency by several orders of magnitude through established engineering procedures. This possibility resulted in a decreased quantity of antibodies necessary for therapy thus making non- intravenous delivery of potent neutralizing mAbs possible.Among the many therapeutic options available, mAbs offer a series of advantages. First, they are the ones that can be developed in the shortest period of time. In fact, the extensive clinical experience with the safety of more than 50 commercial mAbs approved to treat cancer, inflammation and autoimmunity provides high confidence on their safety, support the possibility of having an accelerated regulatory pathway. In addition, the long industrial experience in developing and manufacturing mAbs decreases the risks usually associated with technical development of investigational products. Finally, the incredible technical progress in the field allows to shorten the conventional timelines and go from discovery to proof of concept trials in 5-6 months. Several candidates are presently under development in the field of HIV, pandemic influenza, RSV and many other infectious diseases. Perhapsthe most striking demonstration of the power of mAbs for emerging infections came from the Ebola experience. In this case rapidly developed potent mAbs were among the first drugs to be tested in the Ebola outbreak and showed remarkable efficacy in preventing mortality. Given the striking efficacy of this intervention, potent mAbs became the first, and, so far, the only drug to be recommended for Ebola by the World Health Organization (WHO).Coronaviridae family comprises a large number of virus species that are further classified in four genera. Seven species are of human interest and are highly diversified in terms of adaptation, pathogenicity and diffusion. Indeed, four species are endemic and highly adapted to humans; the recently emerged and currently circulating SARS-CoV-1 and SARS-CoV-2 belong to the same genus (Betacoronavirus) and subgenus (Sarbecovirus) but are phylogenetically distinct and have strikingly different features in terms of infectivity and clinical signs. These aspects demonstrate the difficulties in thoroughly sampling the entire Coronaviridae family necessary to implement an effective surveillance program and therefore stress the need to have therapeutic strategies with broad activity on Coronaviruses. Given the pivotal role of the SARS-CoV-1 and SARS-CoV-2 transmembrane spike glycoprotein (S-protein) for viral pathogenesis, it is considered as the main target to elicit potent neutralizing antibodies and the focus for the development of therapeutic and prophylactic tools against this virus. Indeed, SARS-CoV-1 and SARS-CoV-2 entry into host cells is mediated by the interaction between S-protein and the human angiotensin converting enzyme 2 (ACE2). The S-protein is a trimeric class I viral fusion protein which exists as a metastable pre-fusion conformation and as a stable post-fusion conformation. Each S-protein monomer is composed of two distinct regions, the SI and S2 subunits. Structural rearrangement occurs when the receptor binding domain (RBD) present in the SI subunit binds to the host cell membrane. This interaction destabilizes the pre-fusion state of the S- protein triggering the transition into the post-fusion conformation which in turn results in the entry of the virus particle into the host cell. Single-cell RNA-seq analyses evaluating the expression levels of ACE2 in different human organs has shown that SARS-CoV-2, through S-protein binding, can invade human cells in different major physiological systems including the respiratory, cardiovascular, digestive and urinary systems, enhancing the possibility of spreading and infection. Therapeutic mAbs for COVID-19 treatment have been developed in accelerated time and the pace has been unprecedented for any disease.Nevertheless, it is important to produce neutralizing mAbs or antigen-binding portionthereof that are effective to block the entry process of the virus and its variants and that could have a broader spectrum of neutralizable isolates / species. Accordingly, there is an urgent need for potent, broad spectrum antibody therapeutics with cross-neutralizazion activity against different isolates / species of the coronaviridae family, for use in therapy, prophylaxis, and diagnosis of Coronavirus, in particular SARS-CoV-2 and / or SARS-CoV-1 dependent diseases.Summary of the InventionTo identify potent mAbs against severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), SARS-CoV-2 variants and SARS-CoV-1 the inventors isolated thousands of S- protein specific-memory B cells derived from several people previously infected by SARS- CoV-2 and vaccinated with the coronavirus disease 2019 (COVID-19) BNT162b2 or mRNA-1273 mRNA vaccines. The inventors isolated spike (S) protein specific memory B cells using the recombinant SARS-CoV-1 and SARS-CoV-2 S protein as sorting bait. Naturally produced mAbs were then screened through a microneutralization assay against either the SARS-CoV-1 and SARS-CoV-2. The screening strategy, disclosed in detail in the examples, allowed identification of ten human mAbs that have a potent neutralizing activity against Coronavirus, in particular against SARS-CoV-2 and SARS-CoV-1.In certain aspects, the invention provides a monoclonal antibody or antigen-binding portion thereof capable of neutralizing the biological activity of at least one Coronavirus, which antibody or antigen-binding portion thereof comprises a heavy chain variable domain (VH) and a light chain variable domain (VK) of a monoclonal antibody selected from the group consisting of: 01J19, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13.In certain aspects, the invention provides a monoclonal antibody or antigen-binding portion thereof that specifically binds to S-protein of at least one virus selected from human severe acute respiratory syndrome (SARS) Coronavirus SARS-CoV-2, SARS-CoV-1 and variants thereof, wherein said antibody or antigen-binding portion thereof has a neutralizing activity. In particular, such monoclonal antibody or antigen-binding portion thereof shows 100% inhibitory concentration (ICioo) of less than 100 ng / ml when tested in an in vitro neutralization assay against at least one virus selected from SARS-CoV-1, SARS-CoV-2, and variants thereof,for example against the SARS-CoV-2 Wuhan virus and Omicron variants (BA.5, BA.2.75, BF.7, BQ.1.1 and XBB.1.5).In certain aspects, the invention provides a monoclonal antibody or antigen-binding portion thereof that specifically comprises the VK and VH domains that are at least 85%, 90%, 95%, 97%, 98% or 99% identical in amino acid sequence to the VK and VH domains, respectively, of a monoclonal antibody selected from the group consisting of: 01J19, 02K18, 05F22, 01 J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13.In certain aspects, the invention provides monoclonal antibodies or antigen-binding portion thereof that compete for the binding to the S-protein of at least one Coronavirus, in particular at least one virus selected from SARS-CoV-1, SARS-CoV-2, and variants thereof, with any of the antibodies herein disclosed.In certain aspects, the invention provides monoclonal antibody or an antigen-binding portion according to any embodiments herein disclosed, for use in a prophylactic or therapeutic treatment of a viral infection or conditions or disorders resulting from such infection.In certain aspects, the invention provides monoclonal antibody or an antigen-binding portion according to any embodiments herein disclosed, for use in a prophylactic or therapeutic treatment of an infection from at least one virus selected from SARS-CoV-2, SARS-CoV-1, and variants thereof or conditions or disorders resulting from such infection, in particular Coronavirus disease 2019 (COVID-19).In certain aspects, the invention provides a method of preventing or treating an infection from at least one virus selected from SARS-CoV-1, SARS-CoV-2, and variants thereof or conditions or disorders resulting from such infection, in particular Coronavirus disease 2019 (COVID-19), comprising administering a monoclonal antibody or an antigen-binding portion according to any embodiments herein disclosed, to a subject in need thereof.The invention further provides monoclonal antibody or an antigen-binding portion according to any embodiments herein disclosed for use in the diagnosis, prophylaxis and / or treatment of a subject having, or at risk of developing, a virus infection, in particular a coronavirus infection, more in particular an infection from at least one virus selected from SARS-CoV- 2, SARS-CoV-1, and variants thereof. Furthermore, the invention pertains to the use of the binding molecules and / or the nucleic acid molecules of the invention in the diagnosis / detection of such viral infections.In certain aspects, the invention provides a pharmaceutical composition comprising at leastone or more monoclonal antibodies or antigen-binding portions thereof according to any one of the embodiments herein disclosed and a pharmaceutically acceptable carrier and its use in the prevention and / or treatment of a Coronavirus infection or conditions or disorders resulting from such infection, preferably an infection from at least one virus selected from SARS- CoV-1, SARS-CoV-2, and variants thereof, in particular Coronavirus disease 2019 (COVID-19).In certain aspects, the invention provides an isolated cell line that produces the antibody or antigen-binding portion thereof according to any one of the embodiments herein disclosed.In certain aspects, the invention provides an isolated nucleic acid molecule comprising a nucleotide sequence that encodes the antibody or antigen-binding portion thereof according to any one of the embodiments herein disclosed.In certain aspects, the invention provides a vector comprising the nucleic acid molecule encoding the antibody or antigen-binding portion thereof embodiments according to any one of the embodiments herein disclosed, wherein the vector optionally comprises an expression control sequence operably linked to the nucleic acid molecule.In certain aspects, the invention provides a non-human transgenic animal or transgenic plant comprising the nucleic acid according to any one of the preceding embodiments, wherein the non- human transgenic animal or transgenic plant expresses said nucleic acid. In certain embodiments, said non-human transgenic animal is a mammal.In certain aspects, the invention provides the in vitro or ex vivo use of the monoclonal antibody or an antigen-binding portion thereof according to any one of the embodiments herein disclosed in the diagnosis of a Coronavirus infection, preferably of an infection from at least one virus selected from SARS-CoV-1, SARS-CoV-2, and variants thereof.In certain aspects, the invention provides an in vitro method for revealing the presence of at least one Coronavirus in a sample, preferably of at least one virus selected from SARS-CoV-1, SARS-CoV-2, and variants thereof, comprising the following steps: i) Contacting the antibody or an antigen-binding portion thereof according to any one of the embodiments herein disclosed; ii) Detecting the binding of said antibody or an antigen-binding portion thereof to the S-protein of said at least one Coronavirus.In certain aspects, the invention provides an in vitro method for the diagnosis of a Coronavirus infection in a subject, preferably of an infection from at least one virus selected from SARS-CoV-1, SARS-CoV-2, and variants thereof, comprising the following steps: i) Contacting the antibody or an antigen-binding portion thereof according to any one of the embodiments herein disclosed with a biological sample of said subject; ii) Detecting the binding of said antibody or an antigen-binding portion thereof to the S-protein of said at least one Coronavirus.In certain aspects the invention provides for a diagnostic kit comprising as a specific reagent an antibody or an antigen-binding portion thereof according to any of the embodiments disclosed herein, said kit being intended in particular for use in a method for detecting or quantifying, in a biological sample from a patient, anti-coronavirus antibodies and / or the coronavirus S-protein, in particular anti-SARS-CoV-2 and / or anti-SARS-CoV-1 antibodies, and / or SARS-CoV-2 and / or SARS-CoV-1 S-protein.In certain aspects the invention provides for the use of an antibody or an antigen-binding portion thereof according to any of the embodiments disclosed herein for the design of a vaccine against at least one Coronavirus, in particular against at least one virus selected from SARS-CoV-1, SARS-CoV-2 and variants thereof.In certain aspects the invention provides for a mimotope specifically directed against the idiotype of an antibody or an antigen-binding portion thereof according to any one of the embodiments disclosed herein.In certain aspects the invention provides for an anti-idiotype antibody that is specifically directed against the idiotype of an antibody or an antigen-binding portion thereof according to any one of the embodiments disclosed herein.The invention contemplates combinations of any of the foregoing aspects and embodiments of the invention.Brief description of the drawingsFig. 1 - Characteristic of neutralizing human coronavirus antibodies. The heatmap shows the binding, SARS-CoV-1 and SARS-CoV-2 neutralization activity, and epitope region recognized by the 10 selected nAbs according to the present invention. The potency legend describes exclusively the neutralization activity.Detailed description of the inventionUnless otherwise defined herein, scientific and technical terms used in connection with the present invention shall have the meanings that are commonly understood by those of ordinary skill in the art. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. Generally, nomenclature used in connection with, and techniques of, cell and tissue culture, molecular biology, immunology, microbiology, genetics and protein and nucleic acid chemistry and hybridization described herein are those well-known and commonly used in the art. The methods and techniques of the present invention are generally performed according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification unless otherwise indicated. See, e.g., Sambrook et al. Molecular Cloning: A Laboratory Manual, second ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1989) and Ausubel et al, Current Protocols in Molecular Biology, Greene Publishing Associates (1992), and Harlow and Lane Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1990), incorporated herein by reference.The following terms, unless otherwise indicated, shall be understood to have the following meanings:The term "polypeptide" encompasses native or artificial proteins, protein fragments and polypeptide analogues of a protein sequence. A polypeptide may be monomeric or polymeric. The term "isolated protein", "isolated polypeptide" or "isolated antibody" is a protein, polypeptide or antibody that by virtue of its origin or source of derivation (1) is not associated with naturally associated components that accompany it in its native state, (2) is free of other proteins from the same species, (3) is expressed by a cell from a different species, or (4) does not occur in nature. Thus, a polypeptide that is chemically synthesized or synthesized in a cellular system different from the cell from which it naturally originates will be "isolated" from its naturally associated components. A protein may also be rendered substantially free of naturally-associated components by isolation, using protein purification techniques well known in the art. Examples of isolated antibodies include an anti-SARS- CoV-2 and / or SARS-CoV-1 S-protein antibody that has been affinity purified using SARS- CoV-2 and / or SARS-CoV-1 S-protein or a portion thereof, an anti- SARS-CoV-2 and / or SARS-CoV-1 S-protein antibody that has been synthesized by a hybridoma or other cell line in vitro, and a human anti- SARS-CoV-2 and / or SARS-CoV-1 S-protein antibodyderived from a transgenic animal. A protein or polypeptide is "substantially pure", "substantially homogeneous", or "substantially purified" when at least about 60 to 75% of a sample exhibits a single polypeptide. The polypeptide or protein may be monomeric or multimeric. A substantially pure polypeptide or protein will typically comprise about 50%, 60%, 70%, 80% or 90% W / W of a protein sample, more usually about 95%, and preferably will be over 99% pure. Protein purity or homogeneity may be indicated by a number of means well known in the art, such as polyacrylamide gel electrophoresis of a protein sample, followed by visualizing a single polypeptide band upon staining the gel with a stain well known in the art. For certain purposes, higher resolution may be provided by using HPLC or other means well known in the art for purification. The term "polypeptide fragment" as used herein refers to a polypeptide that has an amino-terminal and / or carboxy-terminal deletion, but where the remaining amino acid sequence is identical to the corresponding positions in the naturally occurring sequence. In some embodiments, fragments are at least 5, 6, 8 or 10 amino acids long. In other embodiments, the fragments are at least 14, at least 20, at least 50, or at least 70, 80, 90, 100, 150 or 200 amino acids long. The term "polypeptide analogue" as used herein refers to a polypeptide that comprises a segment that has substantial identity to a portion of an amino acid sequence and that has at least one of the following properties: (1) specific binding to at least one Coronavirus S-protein under suitable binding conditions, (2) ability to inhibit said at least one Coronavirus S-protein. Typically, polypeptide analogues comprise a conservative amino acid substitution (or insertion or deletion) with respect to the native sequence. Analogues typically are at least 20 or 25 amino acids long, preferably at least 50, 60, 70, 80, 90, 100, 150 or 200 amino acids long or longer, and can often be as long as a full-length polypeptide. Some embodiments of the invention include polypeptide fragments or polypeptide analogue antibodies with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or 17 substitutions from the germline amino acid sequence. In certain embodiments, amino acid substitutions to an anti- Coronavirus S-protein antibody or antigen-binding portion thereof are those which: (1) reduce susceptibility to proteolysis, (2) reduce susceptibility to oxidation, (3) alter binding affinity to form protein complexes, and (4) confer or modify other physicochemical or functional properties of such analogues, but still retain specific binding to at least one Coronavirus S-protein. Analogues can include various muteins of a sequence other than the normally occurring peptide sequence. For example, single or multiple amino acid substitutions, preferably conservative amino acidsubstitutions, may be made in the normally occurring sequence, preferably in the portion of the polypeptide outside the domain(s) forming intermolecular contacts. A conservative amino acid substitution should not substantially change the structural characteristics of the parent sequence; e.g., a replacement amino acid should not alter the anti-parallel [beta]-sheet that makes up the immunoglobulin binding domain that occurs in the parent sequence, or disrupt other types of secondary structure that characterizes the parent sequence. In general, glycine and proline would not be used in an anti-parallel [beta]-sheet. Examples of art- recognized polypeptide secondary and tertiary structures are described in Proteins, Structures and Molecular Principles (Creighton, Ed., W. H. Freeman and Company, New York (1984)); Introduction to Protein Structure (C. Branden and J. Tooze, eds., Garland Publishing, New York, N.Y. (1991)); and Thornton et ai, Nature 354: 105 (1991), incorporated herein by reference.The term “SARS-CoV-1” is for severe acute respiratory syndrome coronavirus (known as SARS-CoV or SARS-CoV-1), which was first identified in southern China in 2002 (World Health Organization 2020). The SARS coronavirus (SARS-CoV) is a member of the Coronaviridae family of enveloped, positive- Stranded RNA viruses, which as a group, have a broad host range. It contains three major structural proteins: spike (S), membrane (M), nucleocapsid (N). Though it has been shown that passive protection from murine hepatitis vims (MHV, aintensively investigated coronavirus), infection has been achieved by administration of mAb specific for all major structural proteins of the virus, the Spike protein (S) is the major antigenic determinant for coronaviruses.The term “SARS-CoV-2” is for severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), the type of coronavirus that causes coronavirus disease 2019 (COVID-19), which was first identified in Wuhan, China in 2019 (World Health Organization 2020).The term “variant” as used herein with respect to the SARS-CoV-1 and / or SARS-CoV-2 virus, is intended to encompass any known variant of said viruses, for example the SARS- CoV-2 Wuhan and Omicron variants such as BA.5, BA.2.75, BF.7, BQ.1.1 and XBB.1.5. Where an "antibody" is referred to herein with respect to the invention, it is normally understood that an antigen-binding portion thereof may also be used. An antigen-binding portion competes with the intact antibody for specific binding. See generally, Fundamental Immunology, Ch. 7 (Paul, W., ed., second ed. Raven Press, N.Y. (1989)) (incorporated by reference in its entirety for all purposes). Antigen-binding portions may be produced byrecombinant DNA techniques or by enzymatic or chemical cleavage of intact antibodies. In some embodiments, antigen-binding portions include Fab, Fab', F(ab')2, Fd, Fv, dAb, and complementarity determining region (CDR) fragments, single-chain antibodies (scFv), chimeric antibodies, diabodies, nanobodies and any polypeptides that contain at least a portion of an antibody that is sufficient to confer specific antigen binding to the polypeptide. From N-terminus to C-terminus, both the mature light and heavy chain variable domains comprise the regions FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4. The assignment of amino acids to each domain herein is in accordance with the definitions of IMGT convention described in Lefranc et al. (2003), Developmental & Comparative Immunology 27.1 (2003): 55-77.As used herein, an antibody that is referred to by number is the same as a monoclonal antibody that is obtained from the well of the plate of the specific sorted B-cell, for example the antibody 01 JI 9 has been obtained from the well JI 9 of the plate with ID 01.As used herein, a Fd fragment means an antibody fragment that consists of the VH and CH 1 domains; an Fv fragment consists of the VK or VL and VH domains of a single arm of an antibody; and a dAb fragment (Ward et al, Nature 341 :544-546 (1989)) consists of a VH domain.In some embodiments, the antibody is a single-chain antibody (scFv) in which a VL or VK and VH domains are paired to form a monovalent molecule via a synthetic linker that enables them to be made as a single protein chain. (Bird et al, Science 242:423-426 (1988) and Huston et al, Proc. Natl Acad. ScL USA 85:5879-5883 (1988)). In some embodiments, the antibodies are diabodies, i.e., are bivalent antibodies in which VH and VL or VK domains are expressed on a single polypeptide chain, but using a linker that is too short to allow for pairing between the two domains on the same chain, thereby forcing the domains to pair with complementary domains of another chain and creating two antigen binding sites. (See e.g., Holliger P. et al, Proc. Natl. Acad. ScL USA 90:6444-6448 (1993), and Poljak R. J. et al, Structure 2: 1121-1123 (1994)). In such embodiments, the CDR(s) may be incorporated as part of a larger polypeptide chain, may be covalently linked to another polypeptide chain, or may be incorporated noncovalently. In embodiments having one or more binding sites, the binding sites may be identical to one another or may be different.In certain preferred aspects of the invention, a monoclonal antibody according to any of the embodiments disclosed in the present specification and in the claims is a human antibody, i.e., a human monoclonal antibody, or an antigen-binding portion thereof.As used herein, the term "human antibody" means any antibody in which the variable and constant domain sequences are human sequences or any of the CDRs of the variable domain sequences are human sequences. The term encompasses antibodies with sequences derived from human genes, but which have been changed, e.g. to decrease possible immunogenicity, increase affinity, eliminate cysteines that might cause undesirable folding, etc. The term encompasses such antibodies produced recombinantly in non-human cells, which might impart glycosylation not typical of human cells. The term "chimeric antibody" as used herein means an antibody that comprises regions from two or more different antibodies.The term "epitope" includes any protein determinant capable of specific binding to an immunoglobulin or T-cell receptor or otherwise interacting with a molecule. Epitopes or antigenic determinants generally consist of chemically active surface groupings of molecules such as amino acids or carbohydrate or sugar side chains and generally have specific three- dimensional structural characteristics, as well as specific charge characteristics. An epitope may be "linear" or "conformational." In a linear epitope, all of the points of interaction between the protein and the interacting molecule (such as an antibody) occur linearly along the primary amino acid sequence of the protein. In a conformational epitope, the points of interaction occur across amino acid residues on the protein that are separated from one another.A "neutralizing antibody" (also herein abbreviated as nAb), an antibody with "neutralizing activity", or an antibody “capable of neutralizing the biological activity” as used herein means an antibody that neutralizes a biological effect that its target (e.g., a pathogen or an infectious particle) may have. A "neutralizing antibody", an antibody with "neutralizing activity", or an antibody “capable of neutralizing the biological activity” as used herein is for example an antibody or antigen-binding portion thereof showing a 100% inhibitory concentration (IC100) of at least less than 100 ng / ml, preferably less than 50 ng / ml, more preferably less than 25 ng / ml when tested in an in vitro neutralization assay against at least one Coronavirus, preferably against at least one virus selected from SARS-CoV-1, SARS-CoV-2, and variants thereof, performed for example as disclosed herein in the examples.An antibody is said to specifically bind an antigen when the dissociation constant is for example < 1 mM, preferably < 100 nM and most preferably < 10 nM. The dissociation constant may be measured by any of the methods available in the state of the art as for example using enzyme-linked immunoabsorbent assay (ELISAs), radioimmunoassays (RIAs), flow cytometry, surface plasmon resonance, such as BIACORE(TM). For example, the expression “specifically binds to a region of a Coronavirus Spike (S) protein” as herein means that the antibody or its antigen-binding portion provokes more than 50% inhibition of the interaction between the human ACE2 receptor and the viral Spike protein as measured by the NOB assay as described in the examples.The term "polynucleotide" as referred to herein means a polymeric form of nucleotides of at least 10 bases in length, either ribonucleotides or deoxyribonucleotides or a modified form of either type of nucleotide. The term includes single and double stranded forms.The term "isolated polynucleotide" as used herein means a polynucleotide of genomic, cDNA, or synthetic origin or some combination thereof, which by virtue of its origin the "isolated polynucleotide" (1) is not associated with all or a portion of a polynucleotides with which the "isolated polynucleotide" is found in nature, (2) is operably linked to a polynucleotide to which it is not linked in nature, or (3) does not occur in nature as part of a larger sequence.The term "naturally occurring nucleotides" as used herein includes deoxyribonucleotides and ribonucleotides. The term "modified nucleotides" as used herein includes nucleotides with modified or substituted sugar groups and the like. The term "oligonucleotide linkages" referred to herein includes oligonucleotides linkages such as phosphorothioate, phosphorodithioate, phosphoroselenoate, phosphorodiselenoate, phosphoroanilothioate, phoshoraniladate, phosphoroamidate, and the like. See e.g., LaPlanche et al., Nucl. Acids Res. 14:9081 (1986); Stec et al, J. Am. Chem. Soc. 106:6077 (1984); Stein et al., Nucl. Acids Res. 16:3209 (1988); Zon et al., Anti-Cancer Drug Design 6:539 (1991); Zon et al.. Oligonucleotides and Analogues: A Practical Approach, pp. 87-108 (F. Eckstein, Ed., Oxford University Press, Oxford England (1991)); U.S. Patent No. 5,151,510; Uhlmann and Peyman, Chemical Reviews 90:543 (1990), the disclosures of which are hereby incorporated by reference. An oligonucleotide can include a label for detection, if desired. "Operably linked" sequences include both expression control sequences that are contiguous with the gene of interest and expression control sequences that act in trans or at a distance to controlthe gene of interest. The term "expression control sequence" as used herein means polynucleotide sequences that are necessary to affect the expression and processing of coding sequences to which they are ligated. Expression control sequences include appropriate transcription initiation, termination, promoter and enhancer sequences; efficient RNA processing signals such as splicing and polyadenylation signals; sequences that stabilize cytoplasmic mRNA; sequences that enhance translation efficiency (i.e., Kozak consensus sequence); sequences that enhance protein stability; and when desired, sequences that enhance protein secretion. The nature of such control sequences differs depending upon the host organism; in prokaryotes, such control sequences generally include promoter, ribosomal binding site, and transcription termination sequence; in eukaryotes, generally, such control sequences include promoters and transcription termination sequence. The term "control sequences" is intended to include, at a minimum, all components whose presence is essential for expression and processing, and can also include additional components whose presence is advantageous, for example, leader sequences and fusion partner sequences. The term "vector", as used herein, means a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. In some embodiments, the vector is a plasmid, i.e., a circular double stranded piece of DNA into which additional DNA segments may be ligated. In some embodiments, the vector is a viral vector, wherein additional DNA segments may be ligated into the viral genome. In some embodiments, the vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). In other embodiments, the vectors (e.g., non-episomal mammalian vectors) can be integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome. Moreover, certain vectors are capable of directing the expression of genes to which they are operatively linked. Such vectors are referred to herein as "recombinant expression vectors" (or simply, "expression vectors").The term "recombinant host cell" (or simply "host cell"), as used herein, means a cell into which a recombinant expression vector has been introduced. It should be understood that "recombinant host cell" and "host cell" mean not only the particular subject cell but also the progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, beidentical to the parent cell, but are still included within the scope of the term "host cell" as used herein.The term "percent sequence identity" in the context of nucleotide or aminoacidic sequences means the residues in two sequences that are the same when aligned for maximum correspondence. The length of sequence identity comparison may be over a stretch of at least about nine nucleotides, usually at least about 18 nucleotides, more usually at least about 24 nucleotides, typically at least about 28 nucleotides, more typically at least about 32 nucleotides, and preferably at least about 36, 48 or more nucleotides. There are a number of different algorithms known in the art which can be used to measure nucleotide sequence identity. For instance, polynucleotide sequences can be compared using FASTA, Gap or Bestfit, which are programs available, provides alignments and percent sequence identity of the regions of the best overlap between the query and search sequences (Pearson, Methods Enzymol. 183:63-98 (1990); Pearson, Methods Mol. Biol. 132: 185-219 (2000); Pearson, Methods Enzymol. 266:227-258 (1996); Pearson, J Mol. Biol 276:71-84 (1998); incorporated herein by reference). The term "substantial similarity" or "substantial sequence similarity," when referring to a nucleic acid or fragment thereof, or aminoacidic means that when optimally aligned with appropriate nucleotide insertions or deletions with another nucleic acid (or its complementary strand), there is nucleotide sequence identity in at least about 85%, preferably at least about 90%, and more preferably at least about 95%, 96%, 97%, 98% or 99% of the nucleotide bases, as measured by any well-known algorithm of sequence identity, such as FASTA, BLAST or Gap, as discussed above. As applied to polypeptides, the term "substantial identity" means that two peptide sequences, when optimally aligned, such as by the programs GAP or BESTFIT using default gap weights as supplied with the programs, share at least 70%, 75% or 80% sequence identity, preferably at least 90% or 95% sequence identity, and more preferably at least 97%, 98% or 99% sequence identity. In certain embodiments, residue positions that are not identical differ by conservative amino acid substitutions. A "conservative amino acid substitution" is one in which an amino acid residue is substituted by another amino acid residue having a side chain R group with similar chemical properties (e.g., charge or hydrophobicity). In general, a conservative amino acid substitution will not substantially change the functional properties of a protein. In cases where two or more amino acid sequences differ from each other by conservative substitutions, the percent sequence identity may be adjusted upwards to correctfor the conservative nature of the substitution. Means for making this adjustment are well- known to those of skill in the art. See, e.g., Pearson, Methods Mol. Biol. 243:307-31 (1994). Examples of groups of amino acids that have side chains with similar chemical properties include 1) aliphatic side chains: glycine, alanine, valine, leucine, and isoleucine; 2) aliphatic- hydroxyl side chains: serine and threonine; 3) amide-containing side chains: asparagine and glutamine; 4) aromatic side chains: phenylalanine, tyrosine, and tryptophan; 5) basic side chains: lysine, arginine, and histidine; 6) acidic side chains: aspartic acid and glutamic acid; and 7) sulphur-containing side chains: cysteine and methionine. Conservative amino acids substitution groups are: valine-leucine-isoleucine, phenylalanine-tyrosine, lysine-arginine, alanine-valine, glutamate-aspartate, and asparagine-glutamine. Alternatively, a conservative replacement is any change having a positive value in the PAM250 log-likelihood matrix disclosed in Gonnet et al, Science 256: 1443-45 (1992), incorporated herein by reference. A "moderately conservative" replacement is any change having a nonnegative value in the PAM250 log-likelihood matrix. Sequence identity for polypeptides is typically measured using sequence analysis software. Protein analysis software matches sequences using measures of similarity assigned to various substitutions, deletions and other modifications, including conservative amino acid substitutions. For instance, GCG contains programs such as "Gap" and "Bestfit" which can be used with default parameters as specified by the programs to determine sequence homology or sequence identity between closely related polypeptides, such as homologous polypeptides from different species of organisms or between a wild type protein and a mutein thereof.As used herein, the terms "label" or "labelled" refers to incorporation of another molecule in the antibody. In one embodiment, the label is a detectable marker, e.g., incorporation of a radiolabelled amino acid or attachment to a polypeptide of biotinyl moieties that can be detected by marked avidin (e.g., streptavidin containing a fluorescent marker or enzymatic activity that can be detected by optical or colorimetric methods). In another embodiment, the label or marker can be therapeutic, e.g., a drug conjugate or toxin. Various methods of labelling polypeptides and glycoproteins are known in the art and may be used.Anti-Coronavirus Antibodies and Characterization ThereofIn one embodiment, the invention provides a monoclonal antibody or antigen-binding portion thereof capable of neutralizing the biological activity of at least one Coronavirus,which antibody or antigen-binding portion thereof comprises a heavy chain variable domain (VH) and a light chain variable domain (VK) of a monoclonal antibody selected from the group consisting of: 01J19, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13.The nucleic acids encoding the variable domain-comprising portions of heavy and light chains (VH and VL) of the antibodies herein noted as 01J19, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13 and the corresponding deduced amino acid sequences can be found in the sequence listing herein enclosed in the description.In certain aspects, the invention provides a monoclonal antibody or antigen-binding portion thereof that is capable of neutralizing the biological activity of at least one Coronavirus comprising: (a) a heavy chain variable domain amino acid sequence that comprises the amino acid sequence of the heavy chain variable domain of an antibody selected from: 01 J19, 02K18, 05F22, 01 J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13; (b) a light chain variable domain amino acid sequence that comprises the amino acid sequence of the light chain variable domain of an antibody selected from: 01 JI 9, 02K18, 05F22, 01 JI 8, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13; (c) a heavy chain variable domain of (a) and a light chain variable domain of (b); or (d) heavy chain and light chain variable domain amino acid sequences comprising the heavy chain and light chain variable domain amino acid sequences, respectively, from the same antibody selected from: 01J19, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13.In certain aspects, the invention provides a monoclonal antibody or an antigen-binding portion thereof that is capable of neutralizing the biological activity of at least one Coronavirus, comprising: (a) a heavy chain variable domain amino acid sequence that comprises the heavy chain CDR1 , CDR2 and CDR3 amino acid sequences of an antibody selected from: 01J19, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13; (b) a light chain variable domain amino acid sequence that comprises the light chain CDR1 , CDR2 and CDR3 amino acid sequences of an antibody selected from: 01 JI 9, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13: (c) a heavy chain variable domain of (a) and a light chain variable domain of (b); or (d) the heavy chain variable domain and light chain variable domain of (c), comprising heavy chain and light chain CDR amino acid sequences from the same antibody selected from: 01J19, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13.In certain aspects, the invention provides a monoclonal antibody or an antigen-binding portion thereof that specifically binds S-protein of at least one Coronavirus, wherein the antibody comprises VH and VL amino acid sequences from an antibody selected from: 01 J19, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13.In certain aspects, the invention provides a monoclonal antibody that is capable of neutralizing the biological activity of at least one Coronavirus, wherein said antibody comprises a heavy chain of an antibody selected from the group consisting of: 01J19, 02K18, 05F22, 01 J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13. In certain aspects, the invention provides a monoclonal antibody that is capable of neutralizing the biological activity of at least one Coronavirus, wherein said antibody comprises a light chain of an antibody selected from the group consisting of 01J19, 02K18, 05F22, 01 JI 8, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13. In certain aspects, the invention provides a monoclonal antibody that is capable of neutralizing the biological activity of at least one Coronavirus, wherein said antibody comprises a heavy chain and a light chain of the same antibody which is selected from the group consisting of 01J19, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13.In certain aspects, the invention provides a monoclonal antibody or antigen-binding portion thereof that is capable of neutralizing the biological activity of at least one Coronavirus comprising VL and VH domains that are at least 85%, 90%, 95%, 97%, 98% or 99% identical in amino acid sequence to the VL and VH domains, respectively, of a monoclonal antibody selected from the group consisting of 01J19, 02K18, 05F22, 01 JI 8, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13.In certain aspects, the invention provides a monoclonal antibody or antigen-binding portion thereof that is capable of neutralizing the biological activity of at least one Coronavirus comprising the light chain and the heavy chain that are at least 85%, 90%, 95%, 97%, 98% or 99% identical in amino acid sequence to the light chain and the heavy chain, respectively, of a monoclonal antibody selected from the group consisting of 01 JI 9, 02K18, 05F22, 01 JI 8, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13.Preferably, a monoclonal antibody according to any of the embodiments disclosed in the present specification and in the claims is a human antibody or a human monoclonal antibody. According to a preferred aspect, a monoclonal antibody or antigen binding portion thereof according to any of the embodiments disclosed in the present specification and in the claimsis capable of neutralizing the biological activity of or exhibits neutralizing activity against at least one Coronavirus selected from SARS-CoV-1, SARS-CoV-2, OC43, HKU1, 229E and NL63, and variants thereof, more preferably at least one Coronavirus selected from SARS-CoV-1, SARS-CoV-2 and variants thereof.In another preferred aspect, a monoclonal antibody or antigen binding portion thereof according to any of the embodiments disclosed in the present specification and in the claims is capable of neutralizing the biological activity of or exhibits neutralizing activity against at least two, at least three, or at least four species belonging to the Coronaviridae family, in particular at least SARS-CoV-2 and SARS-CoV-1.In certain aspects, a monoclonal antibody or antigen binding portion thereof according to any of the embodiments disclosed in the present specification and in the claims specifically binds to a region of the Spike (S) protein of said at least one Coronavirus, in particular the S protein of SARS-CoV-2 and / or SARS-CoV-1, and at least partially inhibits the S-protein binding to a receptor.In one embodiment said region is i) in the SI domain of said S-protein; or (ii) in the S2 domain of said S-protein; or (iii) in the S-protein trimer of said at least one Coronavirus in its pre-fusion conformation or in its post-fusion conformation or a combination of i) with ii) or in a combination of i) with iii) or in a combination of ii) with iii) or a combination of i) with iv) or a combination of ii) with iv).Preferably, said region is the S protein trimer of SARS-CoV-2 and / or SARS-CoV-1 and / or any of their variants. In another aspect, said region is the NTD domain of the S protein of SARS-CoV-2 and / or SARS-CoV-1 and / or any of their variants.In one embodiment, the invention provides a monoclonal antibody or antigen-binding portion that specifically binds to at least one Coronavirus, wherein said antibody or antigenbinding portion thereof elicits equal to or more than 25%, 50%, 60%, 70%, 80%, 90%, 95% or 99% inhibition of the interaction between the human ACE2 receptor and the viral Spike protein of said at least one Coronavirus as measured by a Neutralization of Binding (NOB) assay.In certain aspects, a monoclonal antibody or antigen-binding portion thereof according to any of the embodiments disclosed herein that specifically binds to S-protein of at least one Coronavirus, wherein said antibody or antigen-binding portion thereof has a neutralizing activity. In particular, such monoclonal antibody or antigen-binding portion thereof shows a 100%inhibitory concentration (ICioo) of less than 100 ng / ml, preferably less than 50, 25, 20, 10, 8, 6, 5, 4, 3, 2, or 1 ng / ml, when tested in an in vitro neutralization assay against said at least one Coronavirus, for example against at least one virus selected from SARS-CoV-1, SARS-CoV-2 and variants thereof, at lOOTCIDso viral dose.One type of amino acid substitution that may be made is to change one or more cysteines in the antibody, which may be chemically reactive, to another residue, such as, without limitation, alanine, or serine. In one embodiment, there is a substitution of a non-canonical cysteine. The substitution can be made in a CDR or framework region of a variable domain or in the constant domain of an antibody. In some embodiments, the cysteine is canonical. Another type of amino acid substitution that may be made is to change any potential proteolytic sites in the antibody. Such sites may occur in a CDR or framework region of a variable domain or in the constant domain of an antibody. Substitution of cysteine residues and removal of proteolytic sites may decrease the risk of any heterogeneity in the antibody product and thus increase its homogeneity. Another type of amino acid substitution is to eliminate asparagine-glycine pairs, which form potential deamidation sites, by altering one or both of the residues. In some embodiments, the C-terminal lysine of the heavy chain of the anti-Coronavirus S-protein antibody of the invention is cleaved. In various embodiments of the invention, the heavy and light chains of the anti-Coronavirus S-protein antibodies may optionally include a signal sequence.The class and subclass of the antibodies according to the present invention may be determined by any method known in the art. In general, the class and subclass of an antibody may be determined using antibodies that are specific for a particular class and subclass of antibody. Such antibodies are commercially available. The class and subclass can be determined by ELISA, or Western blot (immunoblot) as well as other techniques. Alternatively, the class and subclass may be determined by sequencing all or a portion of the constant domains of the heavy and / or light chains of the antibodies, comparing their amino acid sequences to the known amino acid sequences of various class and subclasses of immunoglobulins, and determining the class and subclass of the antibodies.In some embodiments, the antibody according to any of the embodiments disclosed herein is an IgG, an IgM, an IgE, an IgA, or an IgD molecule. In one embodiment, the antibody is an IgG and is an IgGl, IgG2, IgG3, IgG4 subclass. In still another embodiment, the human antibody subclass is IgGl.In some embodiments of the invention, the antibodies according to any of the embodiments disclosed herein bind to S-protein of said at least one Coronavirus, and particularly at least one virus selected from SARS-CoV-2, SARS-CoV-1 and variants thereof, with high affinity. In some embodiments, the antibodies according to any of the embodiments disclosed herein bind with high affinity to the protein trimer of SARS-CoV-2 and / or SARS-CoV-1 S-protein. In some embodiments, the antibodies bind to the N-terminal domain or receptor binding domain (RBD) of SARS-CoV-2 and / or SARS-CoV-1 S-protein. In another embodiment, the antibody binds to the SI or S2 domains of SARS-CoV-2 and / or SARS-CoV-1 S-protein. The binding affinity and dissociation rate of an antibody to Coronavirus S-protein can be determined by methods known in the art. The binding affinity can be measured by ELISAs, RIAs, flow cytometry, surface plasmon resonance, such as BIACORE(TM). The dissociate rate can be measured by surface plasmon resonance. Preferably, the binding affinity and dissociation rate is measured by surface plasmon resonance. More preferably, the binding affinity and dissociation rate are measured using BIACORE(TM). One can determine whether an antibody has substantially the same KD as an anti-Coronavirus S-protein antibody by using methods known in the art.The invention further provides a monoclonal antibody that binds to S-protein of at least one Coronavirus, in particular at least one virus selected from SARS-CoV-1, SARS-CoV-2, and variants thereof, and competes or cross-competes with and / or binds the same epitope as an antibody selected from 01 J19, 02K18, 05F22, 01 J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13. If two antibodies reciprocally compete with each other for binding to said S- protein of said at least one Coronavirus, they are said to cross-compete.One can determine whether an antibody binds to the same epitope or cross competes for binding with an anti-S-protein antibody according to the present invention by using methods known in the art. In one embodiment, one allows the antibody of the invention to bind to S- protein of said at least one Coronavirus under saturating conditions and then measures the ability of the test antibody to bind to the S-protein. If the test antibody is able to bind to the S-protein at the same time as the antibody of the present invention, then the test antibody binds to a different epitope as the antibody of the invention. However, if the test antibody is not able to bind to S-protein of said at least one Coronavirus at the same time, then the testantibody binds to the same epitope, an overlapping epitope, or an epitope that is in close proximity to the epitope bound by the antibody according to the present invention, or the binding of the antibody according to the present invention may induce a conformational change in the S-protein of said at least one Coronavirus that prevents or reduces binding of the test antibody. This experiment can be performed using ELISA, RIA, BIACORE(TM), flow cytometry or other methods known in the art.To test whether an antibody according to the present invention cross-competes with another antibody capable of binding to the S protein of said at least one Coronavirus, one may use the competition method described above in two directions i.e. determining if the reference antibody blocks the test antibody and vice versa. In one embodiment, the experiment is performed using ELISA. Methods of determining KD are discussed further below.In another embodiment, the invention provides an antibody that inhibits, blocks, or decreases said Coronavirus S-protein binding to a receptor, in particular, to angiotensin-converting enzyme 2 (ACE2). In another embodiment, the invention provides an antibody that inhibits, blocks, or decreases Coronavirus S-protein-mediated viral entry into cells. In another embodiment, the invention provides an anti- S-protein of SARS-CoV-2 and / or anti-SARS- CoV-1 or variants thereof antibody that inhibits, blocks, or decreases fusion of viral and cell membranes. In another embodiment, the invention provides an antibody that decreases viral load. In another embodiment, the invention provides an antibody that inhibits, blocks, or decreases in severity for any period of time symptoms or conditions resulting from SARS- CoV-2 and / or SARS-CoV-1 infection. In certain embodiments, the invention provides an antibody that inhibits, blocks, or decreases in severity for a day, a week, a month, 6 months, a year, or for the remainder of the subjects’ life symptoms or conditions resulting from SARS-CoV-2 and / or SARS-CoV-1 infection by 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100%. In certain embodiments, the invention provides an antibody that may perform any combination of the preceding embodiments.In certain embodiments, the mAb constant region of the antibodies is modified for half-life extension and reduced risk of Antibody-Dependent Enhancement (ADE) of disease. For example, to enhance the therapeutic activity of mAbs two different and alternative sets of mutations into their constant domains (M252Y / S254T / T256E according to Dall’Acqua et al., 2006; M428L / N434S as reported by Zalevsky et al., 2010) may be applied.In certain embodiments, in order to reduce the risk of Antibody-Dependent Enhancement (ADE) of disease, mutations that abrogate binding to Fc receptors will be introduced in the Fc part of the IgGl molecule as previously described (L234A / L235A as in Hezareh et al., 2001; Beltramello et al., 2010; P329G LALA as in Schlothauer et al., 2016). All of these modifications may be carried out by means of site-directed mutagenesis, for example using the Agilent Quick-Change II Site-Directed Mutagenesis Kit, according to the manufacturer’s recommendations.In certain embodiments, the antibody comprises the variable regions of an antibody selected from 01 J19, 02K18, 05F22, 01 J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13 and a mutant IgGl constant region backbone, which contains one or more of the following groups of mutations: L234A / L235A (as in Hezareh et al., 2001; Beltramello et al., 2010), P329G (as in Schlothauer et al., 2016); M428L / N434S (as in Zalevsky et al., 2010). Preferably the antibody comprises the variable regions of an antibody selected from 01J19, 02K18, 05F22, 01 J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13 and a mutant IgGl constant region backbone, which contains all three groups of such mutations.Nucleic Acids, Vectors, Host Cells, and Recombinant Methods of Making Antibodies Nucleic AcidsThe present invention also encompasses nucleic acid molecules encoding antibodies or antigen-binding portions thereof according to any of the embodiments disclosed herein. In some embodiments, different nucleic acid molecules encode a heavy chain and a light chain of an antibody according to the present invention. In other embodiments, the same nucleic acid molecule encodes a heavy chain and a light chain of an antibody according to the present invention. In one embodiment, the nucleic acid encodes an antibody, or antigen-binding portion thereof, of the invention. In some embodiments, the nucleic acid molecule comprises a nucleotide sequence that encodes a VK amino acid sequence comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 conservative amino acid substitutions and / or 1, 2, or 3 non- conservative substitutions compared to germline. Substitutions may be in the CDR regions, the framework regions, or in the constant domain. In some embodiments, the nucleic acid molecule encodes a VK amino acid sequence comprising one or more variants compared to germline sequence that are identical to the variations found in the VK of one of the antibodies selected from 01 J19, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13.In some embodiments, the nucleic acid molecule encodes at least three amino acid substitutions compared to the germline sequence found in the VK of one of the antibodies selected from 01J19, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13.In some embodiments, the nucleic acid molecule comprises a nucleotide sequence that encodes the VK amino acid sequence of 01J19, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13or a variant or portion thereof. In some embodiments, the nucleic acid encodes an amino acid sequence comprising the light chain CDRs of one of said above-listed antibodies. In some embodiments, said portion is a contiguous portion comprising CDR1-CDR3. In some embodiments, the nucleic acid encodes the amino acid sequence of the light chain CDRs of said antibody. In some embodiments, said portion encodes a contiguous region from CDR1-CDR3 of the light chain of an antibody according to the present invention.In some embodiments, the nucleic acid molecule encodes a VK amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98% or 99% identical to a VK amino acid sequence of a VK region of any one of antibodies 01J19, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13. Nucleic acid molecules of the invention include nucleic acids that hybridize under highly stringent conditions, such as those described above, to a nucleotide sequence encoding the amino acid sequence of a VK region.In another embodiment, the nucleic acid encodes a full-length light chain of an antibody selected 01 J19, 02K18, 05F22, 01 J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13, or a light chain comprising a mutation, such as one disclosed herein.In still another embodiment, the nucleic acid molecule encodes the variable domain of the heavy chain (VH) that comprises a human VH1, VH3 or VH4 family gene sequence or a sequence derived therefrom. In some embodiments, the nucleic acid molecule encodes one or more amino acid mutations compared to the germline sequence that are identical to amino acid mutations found in the VH of one of monoclonal antibodies 01 JI 9, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13.In some embodiments, the nucleic acid molecule comprises a nucleotide sequence that encodes at least a portion of the VH amino acid sequence of a monoclonal antibody selected from monoclonal antibodies 01J19, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13, all three CDR regions, a contiguous portion including CDR1 -CDR3, orthe entire VH region, with or without a signal sequence. In some embodiments, the nucleic acid molecule comprises a nucleotide sequence that encodes the amino acid sequence of one of 01J19, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13, or said sequence lacking the signal sequence. In some preferred embodiments, the nucleic acid molecule comprises at least a portion of the nucleotide sequence of 01J19, 02K18, 05F22, 01 J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13, or said sequence lacking the signal sequence. In some embodiments, said portion encodes the VH region (with or without a signal sequence), a CDR3 region, all three CDR regions, or a contiguous region including CDR1-CDR3.In some embodiments, the nucleic acid molecule encodes a VH amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98% or 99% identical to the VH amino acid sequences of any one of 01J19, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13.Nucleic acid molecules of the invention include nucleic acids that hybridize under highly stringent conditions, such as those described above, to a nucleotide sequence encoding the amino acid sequence of 01J19, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13or that encodes a VH region thereof.In another embodiment, the nucleic acid encodes a full-length heavy chain of an antibody selected from 01J19, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13 or a heavy chain having the amino acid sequence of 01J19, 02K18, 05F22, 01 JI 8, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13 with or without a signal sequence, or a heavy chain comprising a mutation, such as one of the variants discussed herein. Further, the nucleic acid may comprise the nucleotide sequence of 01J19, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13, with or without a signal sequence, or a nucleic acid molecule encoding a heavy chain comprising a mutation, such as one of the variants discussed herein.A nucleic acid molecule encoding the heavy or light chain of an antibody or portions thereof according to the invention can be isolated from any source that produces such antibody. In various embodiments, the nucleic acid molecules are isolated from a B cell isolated from an animal immunized with S-protein of at least one Coronavirus, such as SARS-CoV-2 and / or SARS-CoV-1 or variants thereof or from an immortalized cell derived from such a B cell that expresses or encodes an anti-SARS-CoV-2 and / or SARS-CoV-1 S-protein antibody.Methods of isolating mRNA encoding an antibody are well known in the art. See, e.g., Sambrook et al. The mRNA may be used to produce cDNA for use in the polymerase chain reaction (PCR) or cDNA cloning of antibody genes. In one embodiment, the nucleic acid molecule is isolated from a hybridoma that has as one of its fusion partners a human immunoglobulin-producing cell from a non-human transgenic animal. In an even more preferred embodiment, the human immunoglobulin producing cell is isolated from a XENOMOUSE animal. In another embodiment, the human immunoglobulin-producing cell is from a non-human, non-mouse transgenic animal, as described above. In another embodiment, the nucleic acid is isolated from a non-human, non-transgenic animal. The nucleic acid molecules isolated from a non-human, non-transgenic animal may be used, e.g., for humanized antibodies. In some embodiments, a nucleic acid encoding a heavy chain of an antibody of the invention can comprise a nucleotide sequence encoding a VH domain of the invention joined in-frame to a nucleotide sequence encoding a heavy chain constant domain from any source. Similarly, a nucleic acid molecule encoding a light chain of an antibody of the invention can comprise a nucleotide sequence encoding a VK domain of the invention joined in-frame to a nucleotide sequence encoding a light chain constant domain from any source. In a further aspect of the invention, nucleic acid molecules encoding the variable domain of the heavy (VH) and / or light (VL or VK) chains are "converted" to full- length antibody genes. In one embodiment, nucleic acid molecules encoding the VH or VL or VK domains are converted to full-length antibody genes by insertion into an expression vector already encoding heavy chain constant (CH) or light chain constant (CL) domains, respectively, such that the VH segment is operatively linked to the CH segment(s) within the vector, and / or the VL or VK segment is operatively linked to the CL segment within the vector. In another embodiment, nucleic acid molecules encoding the VH and / or VL or VK domains are converted into full-length antibody genes by linking, e.g., ligating, a nucleic acid molecule encoding a VH and / or VL or VK domains to a nucleic acid molecule encoding a CH and / or CL domain using standard molecular biological techniques. Nucleotide sequences of human heavy and light chain immunoglobulin constant domain genes are known in the art. See, e.g., Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed., NIH Publ. No. 91-3242, 1991. Nucleic acid molecules encoding the full-length heavy and / or light chains may then be expressed from a cell into which they have been introduced and the antibody isolated.The nucleic acid molecules may be used to recombinantly express large quantities of antibodies of the invention. The nucleic acid molecules also may be used to produce chimeric antibodies, bispecific antibodies, single chain antibodies, immunoadhesins, diabodies, mutated antibodies and antibody derivatives, as described further below. If the nucleic acid molecules are derived from a non-human, non-transgenic animal, the nucleic acid molecules may be used for antibody humanization, also as described below.In another embodiment, a nucleic acid molecule of the invention is used as a probe or PCR primer for a specific antibody sequence. For instance, the nucleic acid can be used as a probe in diagnostic methods or as a PCR primer to amplify regions of DNA that could be used, inter alia, to isolate additional nucleic acid molecules encoding variable domains of the antibodies. In some embodiments, the nucleic acid molecules are oligonucleotides. In some embodiments, the oligonucleotides are from highly variable domains of the heavy and light chains of the antibody of interest. In some embodiments, the oligonucleotides encode all or a part of one ormore ofthe CDRs of antibodies 01 JI 9, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13 or variants thereof as described herein.VectorsThe invention provides vectors comprising nucleic acid molecules that encode the heavy chain of an antibody of the invention or an antigen-binding portion thereof. The invention also provides vectors comprising nucleic acid molecules that encode the light chain of such antibodies or antigen-binding portion thereof. The invention further provides vectors comprising nucleic acid molecules encoding fusion proteins, modified antibodies, antibody fragments, and probes thereof. In some embodiments, the antibodies or antigen-binding portions of the invention are expressed by inserting DNAs encoding partial or full-length light and heavy chains, obtained as described above, into expression vectors such that the genes are operatively linked to necessary expression control sequences such as transcriptional and translational control sequences. Expression vectors include plasmids, retroviruses, adenoviruses, adeno-associated viruses (AAV), plant viruses such as cauliflower mosaic virus, tobacco mosaic virus, cosmids, YACs, EBV derived episomes, and the like. The antibody gene is ligated into a vector such that transcriptional and translational control sequences within the vector serve their intended function of regulating the transcription and translation of the antibody gene. The expression vector and expressioncontrol sequences are chosen to be compatible with the expression host cell used. The antibody light chain gene and the antibody heavy chain gene can be inserted into separate vectors. In one embodiment, both genes are inserted into the same expression vector. The antibody genes are inserted into the expression vector by standard methods (e.g., ligation of complementary restriction sites on the antibody gene fragment and vector, or blunt end ligation if no restriction sites are present). A convenient vector is one that encodes a functionally complete human CH or CL immunoglobulin sequence, with appropriate restriction sites engineered so that any VH or VL or VK sequence can easily be inserted and expressed, as described above. In such vectors, splicing usually occurs between the splice donor site in the inserted J region and the splice acceptor site preceding the human C domain, and also at the splice regions that occur within the human CH exons. Polyadenylation and transcription termination occur at native chromosomal sites downstream of the coding regions. The recombinant expression vector also can encode a signal peptide that facilitates secretion of the antibody chain from a host cell. The antibody chain gene may be cloned into the vector such that the signal peptide is linked in-frame to the amino terminus of the immunoglobulin chain. The signal peptide can be an immunoglobulin signal peptide or a heterologous signal peptide (i.e. a signal peptide from a non-immunoglobulin protein). In addition to the antibody chain genes, the recombinant expression vectors of the invention carry regulatory sequences that control the expression of the antibody chain genes in a host cell. It will be appreciated by those skilled in the art that the design of the expression vector, including the selection of regulatory sequences may depend on such factors as the choice of the host cell to be transformed, the level of expression of protein desired, etc. Preferred regulatory sequences for mammalian host cell expression include viral elements that direct high levels of protein expression in mammalian cells, such as promoters and / or enhancers derived from retroviral LTRs, cytomegalovirus (CMV) (such as the CMV promoter / enhancer), Simian Virus 40 (SV40) (such as the SV40 promoter / enhancer), adenovirus, (e.g. the adenovirus major late promoter (AdMLP)), polyoma and strong mammalian promoters such as native immunoglobulin and actin promoters. For further description of viral regulatory elements, and sequences thereof, see e.g., U.S. Patent No. 5,168,062, U.S. Patent No. 4,510,245 and U.S. Patent No. 4,968,615. Methods for expressing antibodies in plants, including a description of promoters and vectors, as well as transformation of plants is known in the art. See, e.g., United States Patent 6,517,529,incorporated herein by reference. Methods of expressing polypeptides in bacterial cells or fungal cells, e.g., yeast cells, are also well known in the art. In addition to the antibody chain genes and regulatory sequences, the recombinant expression vectors of the invention may carry additional sequences, such as sequences that regulate replication of the vector in host cells (e.g., origins of replication) and selectable marker genes. The selectable marker gene facilitates selection of host cells into which the vector has been introduced (see e.g., U.S. Patent Nos. 4,399,216, 4,634,665 and 5,179,017, incorporated herein by reference). For example, typically the selectable marker gene confers resistance to drugs, such as G418, hygromycin or methotrexate, on a host cell into which the vector has been introduced. Preferred selectable marker genes include the dihydrofolate reductase (DHFR) gene (for use in dhfr- host cells with methotrexate selection / amplification), the neo gene (for G418 selection), and the glutamate synthetase gene.Non-Hybridoma Host Cells and Methods of Recombinantly Producing ProteinNucleic acid molecules encoding antibodies and vectors according to the present invention comprising these nucleic acid molecules can be used for transfection or transformation of a suitable mammalian, plant, bacterial or yeast host cell. Transfection or transformation can be by any known method for introducing polynucleotides into a host cell. Methods for introduction of heterologous polynucleotides into mammalian cells are well known in the art and include dextran-mediated transfection, calcium phosphate precipitation, polybrene- mediated transfection, protoplast fusion, electroporation, encapsulation of the polynucleotide(s) in liposomes, and direct microinjection of the DNA into nuclei. In addition, nucleic acid molecules may be introduced into mammalian cells by viral vectors. Methods of transforming cells are well known in the art (see, e.g., U.S. Patent Nos. 4,399,216, 4,912,040, 4,740,461, and 4,959,455, incorporated herein by reference). Methods for transforming plant cells are well known in the art, including, e.g., Agrobacterium- mediated transformation, biolistic transformation, direct injection, electroporation and viral transformation. Methods for transforming bacterial and yeast cells are also well known in the art. Mammalian cell lines available as hosts for expression are well known in the art and include many immortalized cell lines available from the American Type Culture Collection (ATCC). These include, inter alia, Chinese hamster ovary (CHO) cells, N50 cells, SP2 cells, HEK-293T cells, NIH-3T3 cells, HeLa cells, baby hamster kidney (BHK) cells, Africangreen monkey kidney cells (COS), human hepatocellular carcinoma cells (e.g., Hep G2), A549 cells, and a number of other cell lines. Cell lines of particular preference are selected through determining which cell lines have high expression levels. Other cell lines that may be used are insect cell lines, such as Sf9 or Sf21 cells. When recombinant expression vectors encoding antibody genes are introduced into mammalian host cells, the antibodies are produced by culturing the host cells for a period of time sufficient to allow for expression of the antibody in the host cells or, more preferably, secretion of the antibody into the culture medium in which the host cells are grown. Antibodies can be recovered from the culture medium using standard protein purification methods. Plant host cells include, e.g., Nicotiana, Arabidopsis, duckweed, corn, wheat, potato, etc. Bacterial host cells include E. coli and Streptomyces species. Yeast host cells include Schizosaccharomyces pombe, Saccharomyces cerevisiae and Pichia pastoris. Further, expression of antibodies of the invention from production cell lines can be enhanced using a number of known techniques. For example, the glutamine synthetase gene expression system (the GS system) is a common approach for enhancing expression under certain conditions. The GS system is discussed in whole or part in connection with European Patent Nos. 0216 846, 0 256 055, 0 323 997 and 0338 841. It is likely that antibodies expressed by different cell lines or in transgenic animals will have different glycosylation from each other. However, all antibodies encoded by the nucleic acid molecules provided herein, or comprising the amino acid sequences provided herein are part of the instant invention, regardless of the glycosylation of the antibodies.Transgenic Animals and PlantsMonoclonal antibodies of the invention also can be produced transgenically through the generation of a mammal or plant that is transgenic for the immunoglobulin heavy and light chain sequences of interest and production of the antibody in a recoverable form therefrom. In connection with the transgenic production in mammals, antibodies of the invention can be produced in, and recovered from, the milk of goats, cows, or other mammals. See, e.g., U.S. Patent Nos. 5,827,690, 5,756,687, 5,750,172, and 5,741,957, incorporated herein by reference. In some embodiments, non- human transgenic animals that comprise human immunoglobulin loci are immunized with S-protein of at least one Coronavirus, such as at least one Coronavirus according to any of the variants disclosed herein or an immunogenicportion thereof, as described above. Methods for making antibodies in plants are described, e.g., in U.S. patents 6,046,037 and 5,959,177, incorporated herein by reference.In some embodiments, non-human transgenic animals or plants are produced by introducing one or more nucleic acid molecules encoding an antibody of the invention into the animal or plant by standard transgenic techniques. See Hogan and United States Patent 6,417,429, supra. The transgenic cells used for making the transgenic animal can be embryonic stem cells or somatic cells or a fertilized egg. The transgenic non-human organisms can be chimeric, nonchimeric heterozygotes, and nonchimeric homozygotes. See, e.g., Hofian et al. Manipulating the Mouse Embryo: A Laboratory Manual second ed., Cold Spring Harbor Press (1999); Jackson et al, Mouse Genetics and Transgenics: A Practical Approach, Oxford University Press (2000); and Pinkert, Transgenic Animal Technology: A Laboratory Handbook, Academic Press (1999), all incorporated herein by reference. In some embodiments, the transgenic non-human animals have a targeted disruption and replacement by a targeting construct that encodes a heavy chain and / or a light chain of interest. In one embodiment, the transgenic animals comprise and express nucleic acid molecules encoding heavy and light chains that specifically bind to S-protein of said at least one Coronavirus, and preferably to (i) the SI domain of SARS-CoV-2 and / or SARS-CoV-1 S-protein; (ii) the S2 domain of SARS-CoV-2 and / or SARS-CoV-1 S-protein; or (iii) both (i) and (ii). In one embodiment, the transgenic animals comprise and express nucleic acid molecules encoding heavy and light chains that specifically bind to human SARS-CoV-2 and / or SARS-CoV-1 S-protein or variants thereof. In some embodiments, the transgenic animals comprise nucleic acid molecules encoding a modified antibody such as a single-chain antibody, a chimeric antibody or a humanized antibody. The antibodies of the invention may be made in any transgenic animal. In one embodiment, the non-human animals are mice, rats, sheep, pigs, goats, cattle or horses. The non-human transgenic animal expresses said encoded polypeptides in blood, milk, urine, saliva, tears, mucus and other bodily fluids.Class switchingAnother aspect of the invention provides a method for converting the class or subclass of an antibody of the invention to another class or subclass. In some embodiments, a nucleic acid molecule encoding a VL or VK or VH that does not include sequences encoding CL or CH is isolated using methods well-known in the art. The nucleic acid molecule then isoperatively linked to a nucleotide sequence encoding a CL or CH from a desired immunoglobulin class or subclass. This can be achieved using a vector or nucleic acid molecule that comprises a CL or CH chain, as described above. For example, an anti- SARS- CoV-2 S-protein antibody that was originally IgM can be class switched to an IgG. Further, the class switching may be used to convert one IgG subclass to another, e.g., from IgGl to IgG2. Another method for producing an antibody of the invention comprising a desired isotype comprises the steps of isolating a nucleic acid encoding a heavy chain of an antibody of the invention and a nucleic acid encoding a light chain of an antibody of the invention, isolating the sequence encoding the VH region, ligating the VH sequence to a sequence encoding a heavy chain constant domain of the desired isotype, expressing the light chain gene and the heavy chain construct in a cell, and collecting the antibody with the desired isotype.Modified AntibodiesIn another embodiment, a fusion antibody or immunoadhesin may be made that comprises all or a portion of an antibody of the invention linked to another polypeptide. In one embodiment, only the variable domains of the antibody according to any of the embodiments disclosed herein are linked to the polypeptide. In still another embodiment, the VH domain of an antibody of the invention is linked to a first polypeptide, while the VK domain of an antibody of the invention is linked to a second polypeptide that associates with the first polypeptide in a manner such that the VH and VK domains can interact with one another to form an antigen binding site. In still another embodiment, the VH domain is separated from the VK domain by a linker such that the VH and VL domains can interact with one another (see below under Single Chain Antibodies). The VH-linker-VK antibody is then linked to the polypeptide of interest. The fusion antibody is useful for directing a polypeptide to a Coronavirus S-protein -expressing cell or tissue, such as a cell or tissue expressing the S- protein of SARS-CoV-2 and / or SARS-CoV-1. The polypeptide may be a therapeutic agent, such as a toxin, chemokine or other regulatory protein, or may be a diagnostic agent, such as an enzyme that may be easily visualized, such as horseradish peroxidase. In addition, fusion antibodies can be created in which two (or more) single-chain antibodies are linked to one another. This is useful if one wants to create a divalent or polyvalent antibody on a single polypeptide chain, or if one wants to create a bispecific antibody or nanobody. Tocreate a single chain antibody, (scFv) the VH- and VK-encoding DNA fragments are operatively linked to another fragment encoding a flexible linker, e.g., encoding the amino acid sequence (GIy4 -Ser)3, such that the VH and VK sequences can be expressed as a contiguous single-chain protein, with the VK and VH domains joined by the flexible linker. See, e.g., Bird et al, Science 242:423-426 (1988); Huston et al, Proc. Natl. Acad. ScL USA 85:5879-5883 (1988); McCafferty et al., Nature 348:552-554 (1990). The single chain antibody may be monovalent, if only a single VH and VK are used, bivalent, if two VH and VK are used, or polyvalent, if more than two VH and VK are used. Bispecific or polyvalent antibodies may be generated that bind specifically to SARS-CoV-2 and / or SARS-CoV-1 or variants thereof S-protein and to another molecule. Bispecific antibodies or antigen-binding fragments can be produced by a variety of methods including fusion of hybridomas or linking of Fab' fragments. See, e.g., Songsivilai & Lachmann, Clin. Exp. Immunol. 79: 315-321 (1990), Kostelny et al, J. Immunol. 148: 1547-1553 (1992). In addition, bispecific antibodies may be formed as "diabodies" or "Janusins". In some embodiments, the bispecific antibody binds to two different epitopes of SARS-CoV-2 and / or SARS-CoV-1 S-protein. In some embodiments, the bispecific antibody has a first heavy chain and a first light chain from monoclonal antibody 01 J19, 02K18, 05F22, 01 J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13 and an additional antibody heavy chain and light chain. In some embodiments, the additional light chain and heavy chain also are from one of the above-identified monoclonal antibodies, but are different from the first heavy and light chains. In some embodiments, the modified antibodies described above are prepared using one or more of the variable domains or CDR regions from a monoclonal antibody provided herein.Derivatized and Labelled AntibodiesAn antibody or antigen-binding portion of the invention can be derivatized or linked to another molecule (e.g., another peptide or protein). In general, the antibodies or portion thereof are derivatized such that the neutralizing activity against said at least one Coronavirus is not affected adversely by the derivatization or labelling. Accordingly, the antibodies and antibody portions of the invention are intended to include both intact and modified forms of the antibodies described herein. For example, an antibody or antibody portion of the invention can be functionally linked (by chemical coupling, genetic fusion, noncovalent association or otherwise) to one or more other molecular entities, such asanother antibody (e.g., a bispecific antibody or a diabody), a detection agent, a cytotoxic agent, a pharmaceutical agent, and / or a protein or peptide that can mediate association of the antibody or antibody portion with another molecule (such as a streptavidin core region or a polyhistidine tag). One type of derivatized antibody is produced by crosslinking two or more antibodies (of the same type or of different types, e.g., to create bispecific antibodies). Suitable crosslinkers include those that are heterobifunctional, having two distinctly reactive groups separated by an appropriate spacer (e.g., m-maleimidobenzoyl-N- hydroxysuccinimide ester) or homobifunctional {e.g., disuccinimidyl suberate). Such linkers are available from Pierce Chemical Company, Rockford, II.

[0179] , Another type of derivatized antibody is a labelled antibody. Useful detection agents with which an antibody or antigen-binding portion of the invention may be derivatized include fluorescent compounds, including fluorescein, fluorescein isothiocyanate, rhodamine, phycoerythrin, 5- dimethylamine-l-napthalenesulfonyl chloride, lanthanide phosphors and the like. An antibody can also be labelled with enzymes that are useful for detection, such as horseradish peroxidase, [beta]-galactosidase, luciferase, alkaline phosphatase, glucose oxidase and the like. When an antibody is labelled with a detectable enzyme, it is detected by adding additional reagents that the enzyme uses to produce a reaction product that can be discerned. For example, when the agent horseradish peroxidase is present, the addition of hydrogen peroxide and diaminobenzidine leads to a coloured reaction product, which is detectable. An antibody can also be labelled with biotin, and detected through indirect measurement of avidin or streptavidin binding. An antibody can also be labelled with a predetermined polypeptide epitope recognized by a secondary reporter (e.g., leucine zipper pair sequences, binding sites for secondary antibodies, metal binding domains, epitope tags). In some embodiments, labels are attached by spacer arms of various lengths to reduce potential steric hindrance. An antibody can also be labelled with a radiolabelled amino acid. The radiolabel can be used for both diagnostic and therapeutic purposes. For instance, the radiolabel can be used to detect SARS-CoV-2 and / or SARS-CoV-1 S-protein-expressing cells ir tumours by x-ray or other diagnostic techniques. Further, the radiolabel can be used therapeutically as a toxin for cancerous cells or tumours. In some embodiments, the antibody can be labelled with a paramagnetic, radioactive or florigenic ion that is detectable upon imaging. In some embodiments, the paramagnetic ion is chromium (III), manganese (II), iron (III), iron (II), cobalt (II), nickel (II), copper (II), neodymium (III), samarium (III), ytterbium (III),gadolinium (III), vanadium (II), terbium (III), dysprosium (III), holmium (III) or erbium (III). In other embodiments, the radioactive ion is iodine 123, technetium 99, indium 111, rhenium 188, rhenium 186, copper 67, iodine 131, yttrium90, iodine 125, astatine 211, and gallium 67. In other embodiments, the antibody of the invention is labelled with an X-ray imaging agent such as lanthanum (III), gold (III) lead (II) and bismuth (III).Compositions and KitsThe invention relates to compositions comprising any of the antibodies or antigen binding portions thereof of the invention and one or more pharmaceutical acceptable excipients and / or carriers.In certain embodiments, the composition may comprise antibodies or a binding portion thereof of any of the preceding embodiments. In some embodiments, the subject of treatment is a human. In other embodiments, the subject is a veterinary subject. In some embodiments, an antagonist anti-SARS-CoV-2 and / or SARS-CoV-1 S-protein antibody that binds to the SI domain and one that binds to the S2 domain or antigen-binding portions of either or both, are both administered to a subject, either together or separately. In certain embodiments the antibodies are in a composition comprising a pharmaceutically acceptable carrier. In another embodiment, one or more of the antagonist antibodies of the invention are administered in combination with one or more additional antagonistic antibodies that bind different epitopes on the S-protein of at least one Coronavirus, that bind the S-protein from different isolates of SARS-CoV-2 and / or SARS-CoV-1 and / or that bind different stages of SARS-CoV-2 and / or SARS-CoV-1 or variants thereof (i.e., early, middle or late stage virus). As used herein, "pharmaceutically acceptable carrier" means any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like that are physiologically compatible. Some examples of pharmaceutically acceptable carriers are water, saline, phosphate buffered saline, dextrose, glycerol, ethanol and the like, as well as combinations thereof. In many cases, it will be preferable to include isotonic agents, for example, sugars, polyalcohols such as mannitol, sorbitol, or sodium chloride in the composition. Additional examples of pharmaceutically acceptable substances are wetting agents or minor amounts of auxiliary substances such as wetting or emulsifying agents, preservatives or buffers, which enhance the shelf life or effectiveness of the antibody. The compositions of this invention may be in a variety of forms, for example, liquid, semi-solid and solid dosage forms, such as liquid solutions (e.g., injectable and infusible solutions),dispersions or suspensions, tablets, pills, powders, liposomes and suppositories. The preferred form depends on the intended mode of administration and therapeutic application. Typical preferred compositions are in the form of injectable or infusible solutions, such as compositions similar to those used for passive immunization of humans. The preferred mode of administration is parenteral (e.g., intravenous, subcutaneous, intraperitoneal, intramuscular). In one embodiment, the antibody is administered by intravenous infusion or injection. In still another embodiment, the antibody is administered by intramuscular or subcutaneous injection. Therapeutic compositions are typically sterile and stable under the conditions of manufacture and storage. The composition can be formulated as a solution, microemulsion, dispersion, liposome, or other ordered structure suitable to high drug concentration. Sterile injectable solutions can be prepared by incorporating the antibody according to any of the embodiments of the invention in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the active compound into a sterile vehicle that contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum drying and freeze-drying that yield a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof. The proper fluidity of a solution can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prolonged absorption of injectable compositions can be brought about by including in the composition an agent that delays absorption, for example, monostearate salts and gelatin. The antibodies of the present invention can be administered by a variety of methods known in the art, although for many therapeutic applications, the preferred route / mode of administration is subcutaneous, intramuscular, or intravenous infusion. As will be appreciated by the skilled artisan, the route and / or mode of administration will vary depending upon the desired results. Other modes of administration include intraperitoneal, intrabronchial, transmucosal, intraspinal, intrasynovial, intraaortic, intranasal, ocular, otic, topical and buccal. In certain embodiments, the active compound of the antibody compositions may be prepared with a carrier that will protect the antibody against rapid release, such as a controlled release formulation, including implants, transdermal patches,and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Many methods for the preparation of such formulations are patented or generally known to those skilled in the art. See, e.g., Sustained and Controlled Release Drug Delivery Systems (J. R. Robinson, ed., Marcel Dekker, Inc., New York, 1978). The invention also provides compositions suitable for administration by inhalation, which comprise one or more of any of the antibodies described herein. Any of the antibodies of the invention may be conveniently delivered to a subject in the form of an aerosol spray presentation from pressurized packs or from a nebuliser, with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, di chlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol the dosage unit may be determined by providing a valve to deliver a metered amount. Capsules and cartridges of e.g., gelatin for use in an inhaler or insufflator may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch. Dellamary et al. (2004) J Control Release. ;95(3): 489-500 describes formulations for the pulmonary delivery of antibodies. The invention also provides compositions, suitable for administration through the oral mucosa, which comprise one or more of any of the antibodies described herein. Oral transmucosal delivery refers to the delivery of a delivery vehicle across a mucous membrane in the oral cavity, pharyngeal cavity, or esophagus, and may be contrasted, for example, with traditional oral delivery, in which absorption of a drug occurs in the intestine. Accordingly, routes of administration in which the antibodies are absorbed through the buccal, sublingual, gingival, pharyngeal, and / or esophageal mucosa are all encompassed within "oral transmucosal delivery," as that term is used herein. For administration through the transmucosal mucosa, any of the antibody of the invention may be formulated, for example, into chewing gums (see U.S. Pat No. 5,711,961) or buccal patches (see e.g. U.S. Patent No. 5,298,256). The invention also provides compositions suitable for administration through the vaginal mucosa, which comprise one or more of any of the antibodies described herein. The antibodies of the invention may be formulated into a vaginal suppository, foam, cream, tablet, capsule, ointment, or gel. In certain embodiments, the compositions comprising the antibodies are formulated with permeants appropriate to the transmucosal barrier to be permeated. Such penetrants are generally known in the art, and include, for example, for trans mucosal administration bile salts and fusidic acid derivatives. In certain embodiments,an antibody of the invention can be orally administered, for example, with an inert diluent or an assailable edible carrier. The compound (and other ingredients, if desired) can also be enclosed in a hard- or soft-shell gelatine capsule, compressed into tablets, or incorporated directly into the subject's diet. For oral therapeutic administration, the antibodies can be incorporated with excipients and used in the form of ingestible tablets, buccal tablets, troches, capsules, elixirs, suspensions, syrups, wafers, and the like. To administer a compound of the invention by other than parenteral administration, it may be necessary to coat the compound with, or co-administer the compound with, a material to prevent its inactivation. Additional active compounds also can be incorporated into the compositions. In certain embodiments, a neutralizing antibody of the invention is co-formulated with and / or co-administered with one or more additional therapeutic agents, particularly anti-viral agents. These therapeutic agents include, without limitation, antibodies that bind other targets, photosensitizers, androgen, oestrogen, nonsteroidal anti-inflammatory agents, antihypertensive agents, analgesic agents, antidepressants, antibiotics, anticancer agents, anaesthetics, antiemetics, anti-infectants, contraceptives, antidiabetic agents, steroids, antiallergy agents, chemotherapeutic agents, anti-migraine agents, agents for smoking cessation, anti-viral agents, immunosuppressants, thrombolytic agent, cholesterol-lowering agents and anti-obesity agents. Therapeutic agents also include peptide analogues that inhibit S-protein activity of at least one Coronavirus such as SARS-CoV-1 and / or SARS-CoV-2 or variants thereof, antibodies or other molecules that prevent said Coronavirus entry into a cell, including but not limited to preventing S-protein binding to a receptor such as the ACE2 receptor, and agents that inhibit Coronavirus S-protein expression. In one embodiment, the additional agents that inhibit Coronavirus S-protein expression comprise an antisense nucleic acid capable of hybridizing to a Coronavirus S-protein mRNA, such as a hairpin RNA or siRNA, locked nucleic acids (LNA) or ribozymes. Sequence-specific nucleic acids capable of inhibiting gene function by RNA interference are well-known in the art. Such combination therapies may require lower dosages of the neutralizing antibody as well as the co-administered agents, thus avoiding possible toxicities or complications associated with the various monotherapies. In certain specific embodiments, the therapeutic agent(s) that is co-formulated with and / or co-administered with a neutralizing antibody of the invention is an antimicrobial agent. Antimicrobial agents include antibiotics (e.g. antibacterial), antiviral agents, antifungal agents, and anti -protozoan agents. Non-limiting examples of antimicrobialagents are sulfonamides, trimethoprim-sulfamethoxazole, quinolones, penicillins, and cephalosporins. The compositions of the invention may include a "therapeutically effective amount" or a "prophylactically effective amount" of an antibody or antigen-binding portion of the invention. A "therapeutically effective amount" refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired therapeutic result. A therapeutically effective amount of the antibody or antibody portion may vary according to factors such as the disease state, age, sex, and weight of the individual, and the ability of the antibody or antibody portion to elicit a desired response in the individual. A therapeutically effective amount is also one in which any toxic or detrimental effects of the antibody or antibody portion are outweighed by the therapeutically beneficial effects. A "prophylactically effective amount" refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired prophylactic result. Typically, since a prophylactic dose is used in subjects prior to or at an earlier stage of disease, the prophylactically effective amount may be less than the therapeutically effective amount. Dosage regimens can be adjusted to provide the optimum desired response (e.g., a therapeutic or prophylactic response). For example, a single bolus can be administered, several divided doses can be administered over time or the dose can be proportionally reduced or increased as indicated by the exigencies of the therapeutic situation. It is especially advantageous to formulate parenteral compositions in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the mammalian subjects to be treated; each unit containing a predetermined quantity of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The specification for the dosage unit forms of the invention are dictated by and directly dependent on (a) the unique characteristics of the antibody or portion thereof and the particular therapeutic or prophylactic effect to be achieved, and (b) the limitations inherent in the art of compounding such an antibody for the treatment of sensitivity in individuals. An exemplary, non-limiting range for a therapeutically or prophylactically- effective amount of an antibody or antibody portion of the invention is 0.025 to 50 mg / kg, more preferably 0.1 to 50 mg / kg, more preferably 0.1- 25, 0.1 to 10 or 0.1 to 3 mg / kg. In some embodiments, a formulation contains 5 mg / nil of antibody in a buffer of 20mM sodium citrate, pH 5.5, 140mM NaCl, and 0.2mg / ml polysorbate 80. It is to be noted that dosage values may vary with the type and severity ofthe condition to be alleviated. It is to be further understood that for any particular subject, specific dosage regimens should be adjusted over time according to the individual need and the professional judgment of the person administering or supervising the administration of the compositions, and that dosage ranges set forth herein are exemplary only and are not intended to limit the scope or practice of the claimed composition. Another aspect of the present invention provides kits comprising an antibody, or antigen-binding portion, of the invention or a composition comprising such an antibody or antigen-binding fragment. A kit may include, in addition to the antibody or composition, diagnostic or therapeutic agents. A kit can also include instructions for use in a diagnostic or therapeutic method, as well as packaging material such as, but not limited to, ice, dry ice, styrofoam, foam, plastic, cellophane, shrink wrap, bubble wrap, cardboard and starch peanuts. In one embodiment, the kit includes the antibody or a composition comprising it and a diagnostic agent that can be used in a method described below. In still another embodiment, the kit includes the antibody or a composition comprising it and one or more therapeutic agents that can be used in a method described below.In one embodiment the antibodies or binding portion thereof or composition comprising such antibodies according to any one of the embodiments herein disclosed are for use in the prevention or the treatment of patients infected with Coronavirus, in particular infected with SARS-CoV-2 and / or SARS-CoV-1 or variants thereof. The use of such antibodies and compositions of said Abs include, but are not limited to passive immunization in persons at risk of contracting the infection (e.g. professionally exposed personnel, people living in endemic areas) and therapy of acute cases, either hospitalized or not. The invention also relates to compositions for inhibiting viral infection, and in particular Coronavirus infection, more in particular SARS-CoV-2 and / or SARS-CoV-1 or variants thereof infection in a mammal comprising an amount of an antibody of the invention in combination with an amount of an antiviral agent, wherein the amounts of the antibody and of antiviral agent are together effective in inhibiting viral replication, viral infection of new cells or viral loads.Diagnostic Methods of UseThe antibodies according to the invention may use also as diagnostic tools for rapid detection of an infection from at least one coronavirus. In another aspect, the invention provides diagnostic methods. The antibodies according to any of the embodiments of the inventioncan be used to detect S-protein of said at least one Coronavirus, in particular of a virus selected from SARS-CoV-2, SARS-CoV-1 and variants thereof, in a biological sample in vitro, ex-vivo or in vivo. In one embodiment, the invention provides a method for diagnosing the presence or location of said one or more Coronaviruses in a subject in need thereof. The antibodies of the invention can be used in a conventional immunoassay, including, without limitation, an ELISA, an RIA, flow cytometry, tissue immunohistochemistry, Western blot (immunoblot) or immunoprecipitation. The antibodies of the invention can be used to detect Coronavirus S-protein from humans. The invention provides a method for detecting Coronavirus S-protein in a biological sample, in particular S proteins from at least one virus selected from SARS-CoV-2, SARS-CoV-1 and variants thereof, comprising contacting the biological sample with an antibody of the invention and detecting the bound antibody. In one embodiment, the antibody of the invention is directly labelled with a detectable label. In another embodiment, said antibody (the first antibody) is unlabelled and a second antibody or other molecule that can bind the S-protein antibody is labelled. As is well known to one of skill in the art, a second antibody is chosen that is able to specifically bind the particular species and class of the first antibody. For example, if the selected antibody is a human IgG, then the secondary antibody could be an anti-human-IgG. Other molecules that can bind to antibodies include, without limitation, Protein A and Protein G, both of which are available commercially, e.g., from Pierce Chemical Co. Example of biological samples to use in the diagnostic methods herein disclosed are urine, stool, blood, saliva, biopsies, cerebrospinal fluid, nasopharyngeal and oropharyngeal wash, sputum, endotracheal aspirate, bronchoalveolar lavage or other biological samples obtainable from a human subject.Suitable labels for the antibody or secondary antibody have been disclosed supra, and include various enzymes, prosthetic groups, fluorescent materials, luminescent materials and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, [beta]-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin / biotin and avidin / biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol. In other embodiments, S-protein can be assayed in a biological sample by a competition immunoassay utilizing S-protein standards labelled with a detectable substance and an unlabelled antibody of the invention.In this assay, the biological sample, the labelled S-protein standards and the antibody are combined and the amount of labelled S-protein standard bound to the unlabelled antibody is determined. The amount of Coronavirus S-protein in the biological sample is inversely proportional to the amount of labelled S-protein standard bound to the antibody. One can use the immunoassays disclosed above for a number of purposes. For example, the antibodies can be used to detect S-protein in cultured cells or as a diagnostic assay in samples from a subject, in particular S-protein from at least one virus selected from SARS-CoV-2, SARS-CoV-1 and variants thereof. The diagnostic methods according to any embodiments herein disclosed may be followed by a further step of the administration in the positive subject of at least an antibody of the invention, for example according to any of the Therapeutic Methods herein disclosed.Therapeutic Methods of UseIn another embodiment, the invention provides a method for neutralizing at least one Coronavirus, in particular at least one virus selected from SARS-CoV-2, SARS-CoV-1 and variants thereof, by administering an antibody according to any of the embodiments disclosed herein to a patient in need thereof. Any of the types of antibodies described herein may be used therapeutically. In various embodiments, said antibody is a human antibody. In some embodiments, the antibody, or antigen-binding portion thereof, binds to the SI domain of said Coronavirus S-protein. In some embodiments, the patient is a human patient. Alternatively, the patient may be a mammal infected with said at least one Coronavirus, for example infected with at least one virus selected from SARS-CoV-2, SARS-CoV-1 and variants thereof. In one embodiment, the invention provides methods of treating, aiding in the treatment, preventing or aiding in the prevention of an infection from at least one Coronavirus, preferably from at least one virus selected from SARS-CoV-2, SARS-CoV-1 and variants thereof, and conditions or disorders resulting from such infection, in a subject by administering to the subject a therapeutically-effective or prophylactically effective amount of an antibody of the invention. Antibodies and antigen-binding fragments thereof which are antagonists of said Coronavirus S-protein can be used as therapeutics for such infection. The antibody may be administered locally or systemically. The therapeutic compositions comprising one or more antibodies according to any of the embodiments disclosed herein may be administered to the subject, for example, orally, nasally, vaginally,buccally, rectally, via the eye, or via the pulmonary route, in a variety of pharmaceutically acceptable dosing forms, which will be familiar to those skilled in the art. For example, the antibodies may be administered via the nasal route using a nasal insufflator device. The antibodies can also be administered to the eye in a gel formulation. For example, before administration, a formulation containing one or more antibodies according to any of the embodiments disclosed herein may be conveniently contained in a two-compartment unit dose container, one compartment containing a freeze-dried antibody preparation and the other compartment containing normal saline. The dosage of antibody will generally be in the range of 0.1-100 mg / kg, more preferably 0.5-50 mg / kg, more preferably 1-20 mg / kg, and even more preferably 1-10 mg / kg. The serum concentration of the antibody may be measured by any method known in the art.In another embodiment, the antibodies of the present invention are administered to the subject in combination with other therapeutic agents. In one embodiment, the additional therapeutic agents may be treating the symptoms of the Coronavirus infection on their own, and may optionally synergize with the effects of the antibodies. The additional agent that is administered may be selected by one skilled in the art for treating the infection. Coadministration of the antibody with an additional therapeutic agent (combination therapy) encompasses administering a composition comprising the antibody and the additional therapeutic agent as well as administering two or more separate compositions, one comprising the antibody and the other(s) comprising the additional therapeutic agent(s). Further, although co-administration or combination therapy generally means that the antibody and additional therapeutic agents are administered at the same time as one another, it also encompasses instances in which the antibody and additional therapeutic agents are administered at different times. For instance, the antibody may be administered once every three days, while the additional therapeutic agent is administered once daily. Alternatively, the antibody may be administered prior to or subsequent to treatment with the additional therapeutic agent, for example after a patient has failed therapy with the additional agent. Similarly, administration of any of the antibodies of the invention may be administered prior to or subsequent to other therapy.Said antibody and one or more additional therapeutic agents (the combination therapy) may be administered once, twice or at least the period of time until the condition is treated, palliated or cured. Preferably, the combination therapy is administered multiple times. Thecombination therapy may be administered from three times daily to once every six months. The administering may be on a schedule such as three times daily, twice daily, once daily, once every two days, once every three days, once weekly, once every two weeks, once every month, once every two months, once every three months and once every six months, or may be administered continuously via a minipump. The combination therapy may be administered via an oral, mucosal, buccal, intranasal, inhalable, intravenous, subcutaneous, intramuscular, or parenteral. In certain aspects, the invention provides a method for treating, preventing or alleviating the symptoms of at least one Coronavirus mediated disorder, in particular a disorder mediated by a virus selected from SARS-CoV-1 and / or SARS CoV-1 or variants thereof, in a subject in need thereof, comprising the step of administering to said subject an antibody or antigen-binding portion according to any one of the preceding embodiments, further comprising at least one additional therapeutic agent selected from the group consisting of: (a) one or more antibodies from the group consisting of: 01J19, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13: and(b) one or more antibodies that specifically bind said S-protein of a plurality of Coronavirus strains; and / or(c) one or more neutralizing antibodies that do not bind said Coronavirus S-protein; and / or(d) one or more agents that bind Coronavirus S-protein receptor; and / or(e) one or more anti-viral agents.In certain aspects, the invention provides a kit for treating, preventing or alleviating the symptoms of at least one Coronavirus mediated disorder in a subject in need thereof, in particular a disorder mediated by a virus selected from SARS-CoV-1 and / or SARS CoV-1 or variants thereof, comprising a) one or more antibodies from the group consisting of: 01 J19, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13; and(b) one or more antibodies that specifically bind S-protein of a plurality of Coronavirus strains; and / or(c) one or more neutralizing antibodies that do not bind said S-protein; and / or(d) one or more agents that bind Coronavirus S-protein receptor; and / or(e) one or more anti-viral agents.The human monoclonal antibody or antigen-binding portion thereof herein disclosed may also be used advantageously as a diagnostic reagent in an in vitro method for detecting in a biological sample previously obtained from a patient (such as for example a serum, plasma, blood sample or any other suitable biological material, obtained from the patient, preferably a human being) anti-Coronavirus antibodies, in particular SARS-Cov-2 and / or SARS-CoV- 1 antibodies. These antibodies may be found in the biological sample obtained from the patient for instance as a result of a previous exposure to the virus, or because a monoclonal antibody of the invention had been previously administered to the patient for therapeutic or prophylactic or research purposes. Thus, a diagnostic kit comprising the human monoclonal antibody or antigen-binding portion thereof herein disclosed of the invention, as a specific reagent, also falls within the scope of the invention, said kit being in particular designed for the detection and / or quantification, in a biological sample previously obtained from a patient, of anti-coronavirus antibodies.The human monoclonal antibody or antigen-binding portion thereof herein disclosed may also be used advantageously for the design of a vaccine against coronavirus. As disclosed in Rappuoli, Rino et al. “ Reverse vaccinology 2.0: Human immunology instructs vaccine antigen design. ” The Journal of experimental medicine vol. 213,4 (2016): 469-81. doi: 10.1084 / jem.20151960”, human mAb may be used to identify protective antigens / epitopes. Structural characterization of the Ab-antigen complex may be used to instruct antigen design. Thus, also a method or the use of the human monoclonal antibody or antigen-binding portion thereof herein disclosed for the design of a vaccine against a coronavirus, in particular against the SARS-Cov-2 virus, the SARS-CoV-1 virus and / or variants thereof is within the scope of the invention.The human monoclonal antibody or antigen-binding portion thereof herein disclosed may be used for the preparation of mimotopes, such as for example anti-idiotype antibodies, peptides, S-protein truncated or artificial forms or others, endowed with the ability of evoking the antibodies herein disclosed. Among these, the anti-idiotype antibodies are preferred. The anti-idiotype antibodies are antibodies specifically directed against the idiotype of the neutralizing antibodies used for the manufacture thereof, and thus are able to mimic the key epitopes that they recognize. The manufacture of anti-idiotype antibodies is carried out by per se known methodologies that do not need further detailed explanations here. Thus, also mimotopes, preferably anti-idiotype antibodies, directed against an antibodyof the invention fall within the scope of the invention. The human monoclonal antibody or antigen-binding portion thereof herein disclosed may be used for the manufacture of antiidiotype antibodies according to methods per se known. Anti-idiotype antibodies are antibodies specifically directed towards the idiotype of the broad-range neutralizing antibodies used to prepare them, and as such are able to mimic the key epitopes they recognize. Therefore, anti-idiotype antibodies directed against a monoclonal antibody of the invention are also included in the scope of the invention.The following experimental section is provided solely by way of illustration and not limitation and does not intend to restrict the scope of the invention as defined in the appended claims. The claims are an integral part of the description.EXAMPLES1. Materials and MethodsEnrollment of donors and Human peripheral blood mononuclear cells (PBMCs) isolationIn the present study 6 donors were enrolled which were immunized with at least three mRNA vaccine doses and infected at least twice by SARS-CoV-2. This cohort has been named super hybrid immunity (SHI). From these donors human peripheral blood mononuclear cells (PBMCs) were collected which were used to perform single cell sorting of spike (S) protein specific cl ass- switched memory B cells (MBCs). In order to identify broadly reactive human monoclonal antibodies (mAbs) both SARS-CoV-1 and SARS-CoV-2 S proteins were used as sorting bait. From all donors a total of 4,505 S protein specific-MBCs were isolated and were all tested in a cytopathic effect-based neutralization assay (CPE-MN) to identify SARS-CoV-2 neutralizing antibodies (nAbs) and through our pseudotype platform to identify SARS-CoV-1 nAbs. A total of 365 were identified showing different levels of neutralization potency and breadth of coverage against the SARS-CoV-2 Wuhan virus and its variants, and SARS-CoV-1. Out of all identified nAbs, ten antibodies, named herein as 01J19, 02K18, 05F22, 01J18, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13 were selected. To evaluate the breadth of binding of the selected nAbs, antibodies were characterized for their ability to bind to SARS-CoV-2 S protein trimer, receptor binding domain (RBD), N-terminal domain (NTD) and S2 domain, and to the S protein of other human coronaviruses including SARS-CoV-1, OC43, HKU1, 229E and NL63. In addition, nAbs targeting the SARS-CoV-2 S protein RBD, were further characterized throughcompetition assay to identify the epitope region targeted by these antibodies. Herein the specific characteristics of these newly discovered antibodies are reported.Functional characterization of neutralizing human coronavirus nAbsThe ten nAbs that showed broad functional activity were initially characterized for their binding activity to SARS-CoV-2 S protein trimer, receptor binding domain (RBD), N- terminal domain (NTD) and S2 domain, and to the S protein of other human coronaviruses including SARS-CoV-1, OC43, HKU1, 229E and NL63. All antibodies recognized the SARS-CoV-2 S protein trimer. One antibody, 04N13, recognized also the SARS-CoV-2 S protein NTD domain, while the remaining nAbs bound to the RBD (Fig. 1, left panel). Among the 10 antibodies, two, 02G11 and 03007, showed also to recognize the SARS-CoV- 1 S protein (Fig. 1, middle panel). The S proteins of OC43, HKU1, 229E and NL63 were not recognized by any of our antibodies. Following, the neutralization potency of the nAbs against SARS-CoV-1 and SARS-CoV-2 Wuhan and Omicron variants was evaluated. Of the two antibodies able to bind the SARS-CoV-1 S protein, 03007 showed extreme neutralization potency against SARS-CoV-1 with a 50% inhibitory concentration (IC50) of 56.0 ng ml'1(Fig. 1, right panel). Conversely, all nAbs neutralized the SARS-CoV-2 Wuhan virus and Omicron variants (BA.5, BA.2.75, BF.7, BQ.1.1 and XBB.1.5) showing different ranges of neutralization potency (Fig. 1, right panel). The 100% inhibitory concentration (IC100) ranged from 9.4 - 37.7 ng ml'1for 01 J19, 15.5 - 110.8 ng ml'1for 02K18, 9.5 - 167.4 ng ml'1for 05F22, 15.2 - 107.6 ng ml'1for 01 JI 8, 3.0 - 53.5 ng ml'1for 02K05, 4.7 - 3767.5 ng ml'1for 01B20, 126.8 - 405.8 ng ml'1for 02G11, 67.9 - 479.9 ng ml'1for 03007, 21.0 - 627.5 ng ml'1for 05N18, and 11.1 - 97.8 ng ml'1for 02N13, (Fig. 1, right panel).Finally, the nine RBD-targeting nAbs were classified based on their capacity to compete with the Class 1 / 2 J081, Class 3 S3092and Class 4 CR30223antibodies. The majority of antibodies (5 / 9; 55.7%), 01J19, 02K18, 05F22, 01J18 and 02K05, were competing with J08 and therefore targeted the Class 1 / 2 region (Fig. 1, right panel). Following, two antibodies (2 / 9; 22.2%), 02G11 and 03007, and one antibody (1 / 9; 11.1%), 01B20, targeted the Class 4 and Class 3 epitope region respectively. Finally, one antibody (1 / 9; 11.1%), 05N18, did not compete with any of the three antibodies and therefore we were not able to identify the targeted epitope region (Fig. 1, right panel).Genetic characterization of neutralizing human coronavirus nAbsThe genes encoding for the heavy and light chains of 01J19, 02K18, 05F22, 01 JI 8, 02K05, 01B20, 02G11, 03007, 05N18, and 02N13 were characterized. Table 1 lists the full nucleotide and amino acidic sequences of the heavy and light chains of these latter antibodies. Table 2 shows the immunoglobulin heavy chain V, D and J (IGHV; IGHD; IGHJ) and light chain V and J (IGLV; IGLJ) gene rearrangements, length of the complementary determining region 3 (CDR3) of the heavy (H-CDR3) and light (L-CDR3) chains and the heavy and light chain V-gene mutation frequencies (%). Overall, higher level of V-gene mutations in the heavy chains (average 8.35%) compared to the light chains (average 4.08%) were observed. Similarly, longer H-CDR3s were observed (average 16.4 amino acids) compared to L-CDR3s (average 9.70 amino acids) (Table 2). Different heavy and light chain rearrangements were used in the present nAb panel. The majority of nAbs (4 / 10; 40.0%) were encoded by the IGHV3-66 germlines paired with different heavy chain D and J genes, and light chains (Table 2). 02K18 and 05F22 used identical heavy chain V, D and J (IGHV3-66;IGHD1-26;IGHJ4-1), and light chain V and J (IGKV3-15;IGKJ2-1) gene rearrangements with important differences in the CDR3 lengths of both chains (Table 2). Similarly, 02G11 and 03007 shared the same heavy (IGHV1-46;IGHD5-5;IGHJ4-1) and light (IGKV3-D15;IGKJ1-1) chain rearrangements with almost identical CDR3 lengths and V-gene mutation levels. Four antibodies (01J19, 02K05, 01B20 and 02N13) in our panel used heavy V genes different form the rest of nAbs. These included the IGHV4-31 (01J19), IGHV3-53 (02K05), IGHV1-3 (01B20) and IGHV3-48 (02N13) (Table 2).Table 1. Sequences of neutralizing human coronavirus nAbsTable 2. Genetic features of neutralizing human coronavirus nAbsDeclaration according to Art. 170bisIn compliance with Art. 170bis of the Italian code of industrial property, the applicant of the present patent application declares that: 5 -For the biological material, containing microorganisms or genetically modified organisms, object or used in the aforementioned patent application, the obligations deriving from national or Community regulations, and in particular, from the provisions referred to in paragraph 6 of the Legislative Decree of 12 April 2001 n.206 and 8 July 2003 n. 224, 10 concerning these modifications, have been respected; -The donors of the human blood samples used in the present patent application gave their informed written consent. The study was approved by local ethics committees.Sequence Listing in the description>SEQ ID NO: 1 Amino acid sequence of variable domain of Heavy chain of antibody herein defined as 01 JI 9 (01J19 VH)QVQLQQWGPGLVKPSQTLSLACTVSGGSISSGSSYWTWIRQQPGKGLEWIGFIFYSESTHHKFFSGNTYYNPSLKSRVIISVDTSKNQFSLRLNSVTAADTAVYYCAREVGGDFWSDYNMPGDYHQIDVWGKGTTVIVSA>SEQ ID NO:2 Amino acid sequence of variable domain of Heavy chain of antibody herein defined as 02K18 (02K18 VH)QVQLVQSGGGLVQPGGSLRLSCVASEIIVSSNYMSWVRQAPGKRLEWVSALFSGGSTFYADSIKGRFTISRDDSKNTLYLQMNSLRAEDTAVYYCARDLGPVGGSDYWGQ GTHVIVSS>SEQ ID NO: 3 Amino acid sequence of variable domain of Heavy chain of antibody herein defined as 05F22 (05F22_VH)EVQLVESGGGVVQPGGSLRVSCEASEIIVS SNYMSWVRQAPGKGLEWVSTVF SGG STFYAESVKGRFTISTDNSKNTLYLHMNRLRVEDTAVYYCTRDLGVVGGTDYWG QGALVTVSS>SEQ ID NO:4 Amino acid sequence of variable domain of Heavy chain of antibody herein defined as 01 JI 8 (01J18 VH)QVQLVESGGGLVQPGGSLRLSCAASTLTVSRNYMNWVRQAPGTGLEWVSVIYPGGTTYYADSVKGRFTVSRDDSKNILFLQMDSLRVEDTAMYYCSRPIMGATSGMDVWGQGTMVTVSSASTKGPSVFPL>SEQ ID NO: 5 Amino acid sequence of variable domain of Heavy chain of antibody herein defined as 02K05 (02K05_VH)QVQLVESGGGLIQPGGSLRLSCEASEIIVNWNYMSWVRQAPGKGLEWVSIIYSGGSTFYADSVKGRFTISTDKSNNTLYLQMHTLRAEDTAVYYCARTLPQFEGFDIWGQG TMVTVSS>SEQ ID NO: 6 Amino acid sequence of variable domain of Heavy chain of antibody herein defined as 01B20 (01B20 VH)QVQLVQSGDEVKKPGASVKISCKTSGFSLTSHALHWVRQAPGQRLEWMGWIGIS ADEGNTKYSHKFEGRLTISRDTSASTAYMDLSSLSSDDTAMYYCATHSGTYQVDY FDHWGQGTLVTVAS>SEQ ID NO: 7 Amino acid sequence of variable domain of Heavy chain of antibody herein defined as 02G11 (02G11_VH)QVQLVQSGAEVKKPGASVKVSCKAFGYTFSDHYMHWLRQAPGQGPEWMGVVIPINGGTSYAQEFQDRLTVTRDKSTSTVYMELSSLTYEDTAVYYCARDPVGPDNFGY SLLD AK YFFDLWGQGTL VT VS S>SEQ ID NO: 8 Amino acid sequence of variable domain of Heavy chain of antibody herein defined as 03007 (03007 VH)QVQLVQSAAEVKKPGASVKVSCRAFGYTFSDHYMHWLRQAPGQGPEWMGVVIPINGGTTYAQNFQDRLT VTRDKSTS S VYMELS SLTYEDTAVYYC ARDP VGPDNFGY SLLD AK YYFD YWGQGTL VT VS S>SEQ ID NOV Amino acid sequence of variable domain of Heavy chain of antibody herein defined as 05N18 (05N18_VH)QVQLVESGGELVQPGGSLTLSCAASEIVVSLNYMRWVRQAPGKGLEWVSLIYAGGSTFYADSVKGRFTISRDNSKNTLYLQMRSLRVEDSAVYYCARDLVTDGMDVWG QGTTVTVSS>SEQ ID NO: 10 Amino acid sequence of variable domain of Heavy chain of antibody herein defined as 02N13 (02N13_VH)Q VQLVESGGGL VQPGGSLRLSC AASGFHFGTYSFNWVRQ APGKGLEWVS YIS S S S STIFYADSVEGRFTISRDDARGSLFLQMNSLRAEDTAIYYCARDPRYYRDSPYYYP LDSWGQGTLVTVSS>SEQ ID NO: 11 Nucleotide sequence of variable domain of Heavy chain of antibody herein defined as 01 J19 (01J19 VH)CAGGTGCAGCTGCAGCAGTGGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCCCTCGCCTGCACTGTCTCTGGTGGCTCCATCAGCAGTGGTTCTTCCTACTGGACCTGGATCCGCCAGCAGCCAGGGAAGGGCCTGGAGTGGATTGGGTTCATCTTTTACAGCGAGAGCACCCACCACAAGTTTTTCAGTGGGAACACCTACTACAACCCGTCCCTCAAGAGTCGAGTGATCATTTCAGTAGACACGTCTAAGAACCAGTTCTCCCTGAGGCTGAACTCCGTGACTGCCGCGGACACGGCCGTGTATTACTGTGCGAGAGAGGTAGGCGGCGATTTTTGGAGTGATTATAACATGCCCGGGGACTACCACCAGATTGACGTCTGGGGCAAAGGGACCACGGTCATCGTCTCCGCA>SEQ ID NO: 12 Nucleotide sequence of variable domain of Heavy chain of antibody herein defined as 02K18 (02K18 VH)CAGGTGCAGCTGGTGCAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGTAGCCTCTGAAATCATCGTCAGTAGCAACTACATGAGTTGGGTCCGCCAGGCTCCAGGGAAGAGGCTGGAGTGGGTCTCAGCTCTTTTTAGTGGAGGCAGCACTTTCTACGCAGACTCCATAAAGGGCAGATTCACCATCTCCAGAGACGATTCCAAGAACACACTGTATCTTCAAATGAACAGTCTGAGAGCCGAAGACACGGCTGTGTATTACTGTGCGAGAGATCTCGGTCCGGTGGGAGGTTCTGACTACTGGGGCCAGGGAACCCACGTCATCGTCTCCTCA>SEQ ID NO: 13 Nucleotide sequence of variable domain of Heavy chain of antibody herein defined as 05F22 (05F22_VH)GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTAGTCCAGCCTGGGGGGTCCCTGAGAGTCTCCTGTGAAGCCTCCGAAATCATCGTCAGCAGCAACTACATGAGTTGGGTCCGCCAGGCTCCAGGAAAGGGGCTGGAGTGGGTCTCAACTGTTTTTAGTGGTGGCAGCACATTTTATGCTGAGTCCGTGAAGGGCAGATTCACCATCTCCACAGACAATTCCAAGAACACGCTGTATCTTCACATGAACAGGCTGAGAGTCGAAGACACGGCTGTCTACTATTGTACGAGAGATCTCGGTGTGGTGGGAGGAACTGATTACTGGGGCCAGGGAGCCCTGGTCACCGTCTCCTCA>SEQ ID NO: 14 Nucleotide sequence of variable domain of Heavy chain of antibody herein defined as 01 J18 (01J18 VH)CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGCTCCCTGAGACTCTCCTGTGCAGCCTCTACACTCACCGTCAGTAGAAACTACATGAACTGGGTCCGCCAGGCTCCAGGGACGGGGCTGGAGTGGGTCTCGGTGATCTATCCCGGTGGTACGACATATTATGCAGACTCCGTGAAGGGCAGATTCACCGTCTCCAGAGACGATTCCAAGAACATACTGTTTCTTCAAATGGACAGTCTGAGGGTCGAGGACACGGCTATGTATTACTGTTCGAGACCAATAATGGGAGCTACTTCGGGTATGGACGTGTGGGGCCAAGGGACCATGGTCACCGTCTCCTCTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGC>SEQ ID NO: 15 Nucleotide sequence of variable domain of Heavy chain of antibody herein defined as 02K05 (02K05_VH)CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGATCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGAAGCCTCTGAAATCATCGTCAATTGGAACTACATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAATTATTTATAGTGGAGGAAGCACATTCTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCACCGACAAATCCAACAACACGCTGTATCTTCAAATGCACACCCTGAGAGCCGAGG ACACGGCCGTGTATTACTGTGCGAGGACCCTCCCGCAGTTTGAAGGTTTTGATA TATGGGGCCAAGGGACAATGGTCACCGTCTCTTCA>SEQ ID NO: 16 Nucleotide sequence of variable domain of Heavy chain of antibody herein defined as 01B20 (01B20 VH)CAGGTGCAGCTGGTGCAGTCTGGGGATGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGATTTCCTGCAAGACTTCTGGATTCAGCCTCACTAGCCATGCTCTGCATTGGGTGCGCCAGGCCCCCGGACAAAGGCTTGAGTGGATGGGATGGATCGGGATCAGCGCTGATGAGGGTAACACAAAATATTCACATAAATTCGAGGGCAGACTCAC CATTTCCAGGGACACATCCGCGAGCACAGCCTACATGGACCTGAGCAGCCTGA GCTCTGACGACACGGCTATGTATTACTGTGCAACACATAGTGGGACCTACCAAGTTGACTACTTTGACCACTGGGGCCAGGGAACCCTGGTCACCGTCGCCTCA >SEQ ID NO: 17 Nucleotide sequence of variable domain of Heavy chain of antibody herein defined as 02G11 (02G11_VH)CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTAAAGAAGCCTGGGGCCTCAGTGAAGGTTTCCTGCAAGGCATTTGGATACACCTTCAGCGACCACTATATGCACTGGCTGCGACAGGCCCCTGGACAGGGGCCTGAGTGGATGGGAGTAGTCATCCCTATTAATGGTGGCACAAGTTACGCACAGGAGTTCCAGGACAGACTCACCGTGAC CAGGGACAAGTCGACCAGCACAGTCTACATGGAGCTGAGCAGCCTGACATATG AAGACACGGCCGTCTATTACTGTGCGAGAGATCCAGTGGGGCCGGACAACTTTGGTTACTCTCTGTTGGACGCCAAATACTTCTTTGACCTCTGGGGCCAGGGGACC CTGGTCACCGTCTCCTCA>SEQ ID NO: 18 Nucleotide sequence of variable domain of Heavy chain of antibody herein defined as 03007 (03007 VH)CAGGTGCAGCTGGTGCAGTCTGCGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTTTCCTGCAGGGCATTTGGATACACCTTCAGCGACCACTATATGCACTGGCTGCGACAGGCCCCTGGACAGGGGCCTGAGTGGATGGGAGTAGTCATCCCTATTAATGGTGGCACAACTTACGCACAGAACTTCCAGGACAGACTCACCGTGAC CAGGGACAAGTCGACCAGCTCAGTCTACATGGAGCTGAGCAGCCTGACATATG AAGACACGGCCGTCTATTACTGTGCGAGAGATCCGGTGGGGCCGGACAACTTTGGTTACTCTCTGTTGGACGCCAAATACTACTTTGACTACTGGGGCCAGGGAAC CCTGGTCACCGTCTCCTCA>SEQ ID NO: 19 Nucleotide sequence of variable domain of Heavy chain of antibody herein defined as 05N18 (05N18_VH)CAGGTGCAGCTGGTGGAGTCTGGGGGAGAGTTGGTCCAGCCGGGGGGGTCCCT GACCCTCTCCTGTGCAGCCTCTGAAATCGTCGTCAGTCTCAATTACATGAGGTG GGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCACTTATTTATGCCG GTGGCAGTACATTCTACGCGGACTCCGTGAAGGGAAGATTCACCATCTCCAGAGACAATTCCAAGAACACACTGTATCTTCAAATGAGAAGCCTGAGAGTTGAGGA CTCGGCTGTATATTACTGTGCGAGAGATCTGGTTACCGACGGTATGGACGTCTG GGGCCAAGGGACCACGGTCACCGTCTCCTCA>SEQ ID NO:20 Nucleotide sequence of variable domain of Heavy chain of antibody herein defined as 02N13 (02N13_VH)CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCCACTTCGGCACCTACAGTTTCAACTGGGTCCGCCAAGCTCCAGGGAAGGGGCTGGAGTGGGTTTCATACATTAGTAGTA GCAGTAGTACCATTTTCTACGCAGACTCTGTGGAGGGCCGATTCACCATCTCCA GAGACGATGCCAGGGGCTCTCTGTTTCTGCAAATGAACAGCCTGAGAGCGGAG GACACGGCTATCTATTACTGTGCGAGAGACCCCCGATATTATCGTGATAGTCC TTATTATTACCCCCTTGACTCTTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA>SEQ ID NO:21 Aminoacidic sequence of variable domain of Light chain of antibody herein defined as 01 J19 (01J19_Vk)DIVMTQSPLSLPVTPGEPASISCRSSQNLLQSNGHNYLDWYLQKPGQSPQLLIYLSS NRASGVPDRFSGSGSGTHFTLKISRVEAEDVGVYYCMQALQTPRTFGQGTKVEIK >SEQ ID NO:22 Aminoacidic sequence of variable domain of Light chain of antibody herein defined as 02K18 (02K18_Vk)EIVMTQSPVTLSVSPGARVTLSCRASQSVSSNLAWYQQKPGQAPRLLIYGASTRAT GVPARFSGSGSETEFSLTISSLQSEDFAIYFCQQYDNWPPDYTFGQGTKLEIK>SEQ ID NO:23 Aminoacidic sequence of variable domain of Light chain of antibody herein defined as 05F22 (05F22_Vk)EIVMTQSPVTLSVSPGERATLSCRASQSVYSNLAWYQQKPGQAPRLLIYEASTRAT DIPARFSGSGSGTDFTLTISSLQSEDFAIYFCQQYTNWPPGYTFGQGTKLEIK>SEQ ID NO:24 Aminoacidic sequence of variable domain of Light chain of antibody herein defined as 01 J18 (01J18_Vk)AIQMTQSPSSLSASVGDRVTIHCQASQDINNYLNWYQQKPGKAPQLLIYDASNLETGVPSRFSGSGSGTYFTFTISSLQPEDIATYYCQQHDNIPPTFGQGTKVEIK>SEQ ID NO:25 Aminoacidic sequence of variable domain of Light chain of antibody herein defined as 02K05 (02K05_Vk)AIQMTQSPSSLSASVGDRVTITCRASQGISTFLNWYQQKPGKAPKLLIYSASSLHSGVPSRFSGSGSGTDFTLTISNLQPEDFATYYCQQSDSTPLYTFGQGTMLEIK>SEQ ID NO:26 Aminoacidic sequence of variable domain of Light chain of antibody herein defined as 01B20 (01B20_Vk)AIQMTQSPSTLSASVGDRVTITCRASQSINNWLAWYQQKPGKAPKLLIFDVSSLDSGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNGYPWTFGQGTKVEIK>SEQ ID NO:27 Aminoacidic sequence of variable domain of Light chain of antibody herein defined as 02G11 (02G1 l_Vk)EIVMTQSPATLSVSPGERATLSCRASHSVGSNLAWYQHKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAIYYCQNYNEWTRTFGQGTKVEVK>SEQ ID NO:28 Aminoacidic sequence of variable domain of Light chain of antibody herein defined as 03007 (03007_Vk)EIVMTQSPATLSVSPGERATLSCRASHSVGSNLAWYQHKPGQAPRLLIYDASTRVTGIPARFSGSGSGTDFTLTISSLQSEDFAIYYCQHYNEWTRTFGQGTKVEIK>SEQ ID NO:29 Aminoacidic sequence of variable domain of Light chain of antibody herein defined as 05N18 (05N18_Vk)AIQMTQSPSFLSASVGDRVTIACRASQGIASSLAWYQQKPGKAPKLLIFAASTLQSGVPSRFSGSGSGTEFALTISGLQPEDFATYYCQQLDASTITFGPGTKVEIK>SEQ ID NO:30 Aminoacidic sequence of variable domain of Light chain of antibody herein defined as 02N13 (02N13_Vk)AIQMTQSPFSLSASVGDRVTITCQASQDITNSLNWFQQKPGKAPNLLIYGASNLETGVSTRFSGSGSGTHFTFTISSLQPEDVATYYCQQYGDFPPYSFGQGTKLEIK>SEQ ID NO:31 Nucleotide sequence of variable domain of Light chain of antibody herein defined as 01 J19 (01J19_Vk)GATATTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTGCAGGTCTAGTCAGAACCTCCTTCAAAGTAATGGACACAACTATTTGGATTGGTACCTGCAGAAGCCAGGGCAGTCTCCACAGCTCCTGATCTATTTGAGTTCTAATCGGGCCTCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCCGGCACACATTTTACACTGAAAATCAGCAGAGTGGAGGCTGAGGATGTTGGGGTTTATTACTGCATGCAAGCTCTACAAACTCCTCGAACGTTCGGCCAAGGGACCAAGGTGGAAATCAAA>SEQ ID NO:32 Nucleotide sequence of variable domain of Light chain of antibody herein defined as 02K18 (02K18_Vk)GAAATTGTGATGACGCAGTCTCCAGTCACCCTGTCTGTGTCTCCAGGGGCAAGAGTCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCACCAGGGCCACTGGTGTCCCAGCCAGGTTCAGTGGCAGTGGGTCTGAGACAGAGTTCAGTCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCTATTTATTTTTGTCAGCAGTATGATAACTGGCCTCCGGACTACACTTTTGGCCAGGGGACCAAGCTGGAGATCAAA>SEQ ID NO:33 Nucleotide sequence of variable domain of Light chain of antibody herein defined as 05F22 (05F22_Vk)GAAATTGTGATGACGCAGTCTCCAGTCACCCTGTCTGTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTTACAGCAACTTAGCCTGGTATCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGAAGCATCCACCCGGGCCACTGATATCCCTGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGACTTTGCAATTTATTTCTGTCAGCAGTATACTAACTGGCCTCCGGGGTACACTTTTGGCCAGGGGACCAAGCTGGAGATCAAA>SEQ ID NO:34 Nucleotide sequence of variable domain of Light chain of antibody herein defined as 01 J18 (01J18_Vk)GCCATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATTCATTGCCAGGCGAGTCAGGACATTAACAACTATTTAAATTGGTATCAACAGAAACCAGGGAAAGCCCCTCAGCTCCTGATCTACGATGCATCCAATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACATATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATATTGCAACATATTACTGTCAACAGCATGATAATATCCCTCCGACGTTCGGCCAAGGGACCAAGGTGGAAATCAA A>SEQ ID NO:35 Nucleotide sequence of variable domain of Light chain of antibody herein defined as 02K05 (02K05_Vk)GCCATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTGGGAGACAGAGTGACCATCACTTGCCGGGCAAGTCAGGGCATTAGCACCTTTTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAACTCCTGATCTATTCTGCATCCAGTTTGCACAGTGGGGTCCCCTCAAGGTTCAGTGGCAGTGGATCTGGAACAGATTTCACTCTCACCATCAGCAATCTGCAACCTGAAGATTTCGCAACTTACTACTGTCAACAGAGTGACAGTACCCCTCTGTACACTTTTGGCCAGGGGACCATGCTGGAGATCAAA>SEQ ID NO:36 Nucleotide sequence of variable domain of Light chain of antibody herein defined as 01B20 (01B20_Vk)GCCATCCAGATGACCCAGTCTCCATCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCCAGTCAGAGTATTAATAACTGGTTGGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTTTGATGTCTCCAGTTTGGACAGTGGGGTCCCATCAAGGTTTAGCGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGTATAATGGTTATCCGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCA AA>SEQ ID NO:37 Nucleotide sequence of variable domain of Light chain of antibody herein defined as 02G11 (02G1 l_Vk)GAAATTGTGATGACGCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCACAGTGTTGGCAGCAACCTAGCCTGGTACCAGCACAAACCTGGCCAGGCTCCCAGACTCCTCATCTATGGTGCATCCACCAGGGCCACTGGCATCCCAGCCAGATTCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCAATTTATTACTGTCAGAACTATAATGAGTGGACACGGACGTTCGGCCAAGGGACCAAGGTGGAAGTCAAA>SEQ ID NO:38 Nucleotide sequence of variable domain of Light chain of antibody herein defined as 03007 (03007_Vk) GAAATTGTGATGACGCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCACAGTGTTGGCAGCAACTTAGCCTGGT ACCAGCACAAACCTGGCCAGGCTCCCAGACTCCTCATCTATGATGCATCCACC AGGGTCACTGGCATCCCAGCCAGATTCAGCGGCAGTGGGTCTGGGACAGACTT CACTCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCAATTTATTACTGTCA GCACTATAATGAGTGGACACGGACGTTCGGCCAAGGGACCAAGGTGGAAATC AAA>SEQ ID NO:39 Nucleotide sequence of variable domain of Light chain of antibody herein defined as 05N18 (05N18_Vk)GCCATCCAGATGACCCAGTCTCCATCCTTCCTGTCTGCATCTGTAGGAGACAGA GTCACCATCGCTTGCCGGGCCAGTCAGGGCATTGCCAGTTCTTTAGCCTGGTAT CAACAAAAACCAGGGAAAGCCCCTAAGCTCCTGATCTTTGCTGCGTCCACTT TGCAAAGTGGAGTCCCATCAAGGTTCAGCGGCAGCGGATCTGGGACAGAATTC GCTCTCACAATCAGCGGCCTGCAGCCTGAAGATTTTGCAACTTATTACTGTCAA CAACTTGATGCTTCCACGATCACTTTCGGCCCTGGGACCAAAGTGGAAATCAA A>SEQ ID NO:40 Nucleotide sequence of variable domain of Light chain of antibody herein defined as 02N13 (02N13_Vk)GCCATCCAGATGACCCAGTCTCCATTCTCCCTGTCTGCATCTGTTGGAGACAGA GTCACCATCACTTGCCAGGCGAGTCAGGACATTACCAACTCTTTGAATTGGTTT CAGCAGAAACCAGGGAAAGCCCCTAACCTCCTGATCTACGGTGCGTCCAATT TGGAAACAGGGGTCTCAACACGGTTCAGTGGAAGTGGATCTGGGACACATTTT ACTTTCACCATCTCCAGCCTGCAGCCTGAAGATGTTGCAACATATTATTGTCAA CAATATGGTGATTTCCCTCCGTACTCTTTTGGCCAGGGGACCAAGCTGGAGAT CAAASequences of the S-proteinSequences of the surface glycoprotein of Severe acute respiratory syndrome coronavirus 2 are known in the art. Sequences of SI (“Spike rec bind”) and S2 (“Coronavirus S2 glycoprotein”) domains are in the GenBank with the ID QHD43416.1.

Claims

CLAIMS1. A monoclonal antibody or antigen-binding portion thereof capable of neutralizing the biological activity of at least one Coronavirus, preferably of at least one virus selected from SARS-CoV-2, SARS-CoV-1 and variants thereof, which antibody or antigen-binding portion thereof comprises a heavy chain variable domain (VH) and a light chain variable domain (VK), wherein: said VH has amino acid sequence set forth in SED ID NO: 1 and said VK has amino acid sequence SED ID NO:21; or said VH has amino acid sequence set forth in SED ID NO:2 and said VK has amino acid sequence SED ID NO:22; or said VH has amino acid sequence set forth in SED ID NO: 3 and said VK has amino acid sequence SED ID NO:23; or said VH has amino acid sequence set forth in SED ID NO:4 and said VK has amino acid sequence SED ID NO:24; or said VH has amino acid sequence set forth in SED ID NO: 5 and said VK has amino acid sequence SED ID NO:25; or said VH has amino acid sequence set forth in SED ID NO: 6 and said VK has amino acid sequence SED ID NO:26; or said VH has amino acid sequence set forth in SED ID NO: 7 and said VK has amino acid sequence SED ID NO:27; or said VH has amino acid sequence set forth in SED ID NO: 8 and said VK has amino acid sequence SED ID NO:28; or said VH has amino acid sequence set forth in SED ID NO: 9 and said VK has amino acid sequence SED ID NO:29; or said VH has amino acid sequence set forth in SED ID NO : 10 and said VK has amino acid sequence SED ID NO:30.

2. The monoclonal antibody or antigen-binding portion thereof according to claim 1, wherein said VL and said VK are at least 85% identical in amino acid sequence, preferably at least 95% identical in amino acid sequence, more preferably at least 98% or at least 99% identical in amino acid sequence of:VH having SED ID NO: 1 and VK having SED ID NO:21; orVH having SED ID NO:2 and VK having SED ID NO:22; orVH having SED ID NO:3 and VK having SED ID NO:23; orVH having SED ID NO:4 and VK having SED ID NO:24; orVH having SED ID NO:5 and VK having SED ID NO:25; orVH having SED ID NO:6 and VK having SED ID NO:26; orVH having SED ID NO:7 and VK having SED ID NO:27; orVH having SED ID NO:8 and VK having SED ID NO:28; orVH having SED ID NO:9 and VK having SED ID NO:29; orVH having SED ID NO: 10 and VK having SED ID NO:30.

3. The monoclonal antibody or antigen-binding portion thereof according to claim 1 or 2, wherein said antibody or antigen-binding portion thereof is a human monoclonal antibody.

4. The monoclonal antibody or an antigen-binding portion thereof according to any one of the claims from 1 to 3, wherein said antibody or antigen-binding portion thereof shows 100% inhibitory concentration (IC100) of less than 100 ng / ml when tested in an in vitro neutralization assay against at least one virus selected from SARS-CoV-2, SARS-CoV-1, and variants thereof.

5. A monoclonal antibody or an antigen-binding portion thereof that competes for the binding to the S protein of at least one Coronavirus with any one of the antibody or antigen-binding portion according to any one of the claims 1 to 4, preferably at least one Coronavirus selected from SARS-CoV-1, SARS-CoV-2, and variants thereof.

6. The monoclonal antibody or an antigen-binding portion thereof according to any one of the claims from 1 to 5, for use in a prophylactic or therapeutic treatment of a virus infection or conditions or disorders resulting from such infection, in particular for use in the prevention and / or treatment of an infection from at least one Coronavirus.

7. The monoclonal antibody or an antigen-binding portion according to any one of the claims from 1 to 6, for use in a prophylactic or therapeutic treatment of infection from at least one virus selected from SARS-CoV-2, SARS-CoV-1, and variants thereof, or conditions or disorders resulting from such infection, in particular Coronavirus disease 2019 (COVID-19).

8. A pharmaceutical composition comprising one or more monoclonal antibody or antigen-binding portion thereof according to any one of the claims from 1 to 7 and a pharmaceutically acceptable carrier.

9. The composition according to claim 8, for use in a prophylactic or therapeutic treatment of a virus infection or conditions or disorders resulting from such infection, in particular for use in the prevention and / or treatment of a Coronavirus infection, more in particular for use in a prophylactic or therapeutic treatment of an infection from at least one virus selected from SARS-CoV-2, SARS-CoV-1, and variants thereof, or conditions or disorders resulting from such infection, in particular for use in the prevention and / or treatment of a SARS-CoV-2 and / or SARS-CoV-1 infection.

10. In vitro or ex vivo use of a monoclonal antibody or an antigen-binding portion thereof according to any one of the claims from 1 to 7 in the diagnosis of an infection from at least one Coronavirus, preferably from atleast one virus selected from SARS-CoV-2, SARS-CoV-1, and variants thereof.

11. An in vitro method for revealing the presence of at least one Coronavirus in a sample comprising the following steps: i) Contacting the antibody or an antigen-binding portion thereof according to any one of the claims from 1 to 7 with said sample; ii) Detecting the binding of said antibody or an antigen-binding portion thereof with the S-protein of said at least one Coronavirus, preferably wherein said Coronavirus is at least one virus selected from SARS-CoV-2, SARS-CoV-1, and variants thereof.

12. An in vitro method for the diagnosis of an infection from at least one Coronavirus in a subject comprising the following steps: i) Contacting the antibody or an antigen-binding portion thereof according to any one of the claims from 1 to 7 with a biological sample of said subject; ii) Detecting the binding of said antibody or an antigen-binding portion thereof with the S-protein of said at least one Coronavirus, preferably wherein said Coronavirus is at least one virus selected from SARS-CoV-2, SARS-CoV-1, and variants thereof.

13. A diagnostic kit comprising as a specific reagent an antibody or an antigen-binding portion thereof according to any one of the claims from 1 to 7, said kit being intended in particular for use in a method for detecting or quantifying, in a biological sample from a patient, anti- coronavirus antibodies and / or the coronavirus S-protein, in particular anti-Sars-Cov-2 and / or anti-SARS-CoV-1 antibodies, and / or SARS-CoV-2 and / or SARS-CoV-1 S-protein.

14. Use of an antibody or an antigen-binding portion thereof according to any one of the claims from 1 to 7 for the design of a vaccine against at least one Coronavirus, in particular against at least one virus selected from SARS-CoV-2, SARS-CoV-1 and variants thereof.

15. A mimotope specifically directed against the idiotype of an antibody or an antigen-binding portion thereof according to any one of the claims from 1 to 7.

16. An anti-idiotype antibody that is specifically directed against the idiotype of an antibody or an antigen-binding portion thereof according to any one of the claims from 1 to 7.

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