Methods and compositions for high-potency polypeptide-based protein inhibition

Abstract

Methods and compositions for polypeptide-based protein inhibition are provided. Aspects of the present disclosure relate to compositions comprising a polypeptide that interacts with a target protein, such as a viral spike protein, or a polynucleotide encoding such a polypeptide, and methods of using them for the treatment and prevention of diseases, such as viral infections and / or post-viral syndromes.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims priority to U.S. Provisional Application Serial No. 63 / 168,107, filed March 30, 2021, which is incorporated herein by reference in its entirety.

[0002] Aspects of the present disclosure relate generally to at least the fields of protein biology, molecular biology, virology, and medicine. [Background technology]

[0003] Proteins are key players in carrying out a vast spectrum of biological functions in a given organism. For example, infections by viruses such as coronaviruses, HIV, Ebola, RSV, and influenza viruses are mediated by the binding of viral spike proteins to receptors on the surface membrane of host cells. Viral infections can cause severe, life-threatening symptoms, such as severe acute respiratory syndrome, Middle East respiratory syndrome, COVID-19, and other respiratory infections, while other symptoms persist and become postviral syndromes. Unfortunately, proteins have not become a primary therapeutic tool in modern medicine. In fact, few therapeutic options for treating these infections have proven effective in robust clinical trials.

[0004] Thus, there is a need for compositions and methods for protein or polypeptide-based therapeutics, particularly for the treatment and prevention of viral infections and / or post-viral syndromes. Summary of the Invention [Means for solving the problem]

[0005] Various aspects of the present disclosure relate to polypeptides that target proteins in vivo, including, but not limited to, viral spike proteins, compositions comprising such polypeptides, and methods of use for the treatment and prevention of diseases or conditions in a subject, including, but not limited to, a coronavirus (e.g., MERS-CoV, SARS-CoV, SARS-CoV-2, HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1) infection, human immunodeficiency virus (HIV) infection, Ebola infection, RSV infection, or influenza infection. In some embodiments, the polypeptide has an amino acid sequence corresponding to the sequence of the target protein, wherein the amino acid sequence has at least 10% sequence identity with the corresponding sequence of the target protein. In some embodiments, the polypeptide has an amino acid sequence corresponding to the oligomerization domain of the target protein, wherein the amino acid sequence has at least 10% sequence identity with the oligomerization domain of the target protein. In some embodiments, the polypeptide comprises an amino acid sequence having at least 10% to 80% identity to SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:25, or SEQ ID NO:34. In some embodiments, the polypeptide has an amino acid sequence corresponding to the oligomerization domain of a coronavirus spike protein, wherein the amino acid sequence has at least 10% to 80% identity to SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16. In some embodiments, the polypeptide has an amino acid sequence corresponding to the sequence of an HIV spike protein, wherein the amino acid sequence has at least 10% to 80% identity to SEQ ID NO:18. In some embodiments, the polypeptide has an amino acid sequence corresponding to the sequence of an Ebola virus glycoprotein, wherein the amino acid sequence has at least 10% to 80% identity to SEQ ID NO:20.In some embodiments, the polypeptide has an amino acid sequence corresponding to the sequence of an influenza virus HA spike protein, wherein the amino acid sequence has at least 10% to 80% identity to SEQ ID NO: 25. In some embodiments, the polypeptide has an amino acid sequence corresponding to the sequence of an RSV glycoprotein, wherein the amino acid sequence has at least 10% to 80% identity to SEQ ID NO: 34.

[0006] Embodiments of the present disclosure include: polypeptides; viral spike proteins; protein interacting polypeptides; viral spike protein interacting polypeptides; coronavirus spike protein interacting polypeptides; MERS-CoV spike protein interacting polypeptides; SARS-CoV spike protein interacting polypeptides; SARS-CoV-2 spike protein interacting polypeptides; HCoV-229E spike protein interacting polypeptides; HCoV-NL63 spike protein interacting polypeptides; HCoV-HKU1 spike protein interacting polypeptides; HCoV-OC43 spike protein interacting polypeptides; HIV spike protein interacting polypeptides; Ebola virus glycoprotein interacting polypeptides; Influenza virus HA spike protein interacting polypeptides; RSV glycoprotein interacting polypeptides;

[0007] vectors encoding polypeptides; vectors encoding protein-interacting polypeptides; vectors encoding viral spike protein-interacting polypeptides; vectors encoding coronavirus spike protein-interacting polypeptides; vectors encoding MERS-CoV spike protein-interacting polypeptides; vectors encoding SARS-CoV spike protein-interacting polypeptides; vectors encoding SARS-CoV-2 spike protein-interacting polypeptides; vectors encoding HCoV-229E spike protein-interacting polypeptides; vectors encoding HCoV-NL63 spike protein-interacting polypeptides; vectors encoding HCoV-HKU1 spike protein-interacting polypeptides; vectors encoding HCoV-OC43 spike protein-interacting polypeptides; vectors encoding HIV spike protein-interacting polypeptides; vectors encoding Ebola virus glycoprotein-interacting polypeptides; vectors encoding influenza virus HA spike protein-interacting polypeptides; vectors encoding RSV glycoprotein-interacting polypeptides;

[0008] Methods for modulating a target protein or its biological function in vivo in a subject; Methods for modulating a viral spike protein or its biological function in vivo in a subject; Methods for modulating a coronavirus spike protein or its biological function in vivo in a subject; Methods for modulating a MERS-CoV spike protein or its biological function in a subject; Methods for modulating a SARS-CoV spike protein or its biological function in vivo in a subject; Methods for modulating a SARS-CoV-2 spike protein or its biological function in vivo in a subject; Methods for modulating an HCoV-229E spike protein or its biological function in vivo in a subject; A method for modulating CoV-NL63 spike protein or its biological function in vivo in a subject; a method for modulating HCoV-HKU1 spike protein or its biological function in vivo in a subject; a method for modulating HCoV-OC43 spike protein or its biological function in vivo in a subject; a method for modulating HIV spike protein or its biological function in vivo in a subject; a method for modulating Ebola virus glycoprotein or its biological function in a subject; a method for modulating influenza virus HA spike protein or its biological function in vivo in a subject; a method for modulating RSV glycoprotein or its biological function in a subject;

[0009] Methods for treating disease; methods for treating viral infections and / or post-viral syndromes; methods for treating coronavirus infections and / or post-coronavirus syndromes; methods for treating MERS-CoV infections; methods for treating SARS-CoV infections; methods for treating SARS-CoV-2 infections; methods for treating HCoV-229E infections; methods for treating HCoV-NL63 infections; methods for treating HCoV-OC43 infections; methods for treating HCoV-HKU1 infections; methods for treating HIV infections; methods for treating Ebola infections; methods for treating influenza infections; methods for treating RSV infections;

[0010] Methods for preventing disease; methods for preventing viral infections and / or post-viral syndromes; methods for preventing coronavirus infections and / or post-coronavirus syndromes; methods for preventing MERS-CoV infections; methods for preventing SARS-CoV infections; methods for preventing SARS-CoV-2 infections; methods for preventing HCoV-229E infections; methods for preventing HCoV-NL63 infections; methods for preventing HCoV-OC43 infections; methods for preventing HCoV-HKU1 infections; methods for preventing HIV infections; methods for preventing Ebola infections; methods for preventing influenza infections; methods for preventing RSV infections;

[0011] Methods for reducing the severity of disease; methods for reducing the severity of viral infections and / or post-viral syndromes; methods for reducing the severity of coronavirus infections and / or post-coronavirus syndromes; methods for reducing the severity of MERS-CoV infections; methods for reducing the severity of SARS-CoV infections; methods for reducing the severity of SARS-CoV-2 infections; methods for reducing the severity of HCoV-229E infections; methods for reducing the severity of HCoV-NL63 infections; methods for reducing the severity of HCoV-OC43 infections; methods for reducing the severity of HCoV-HKU1 infections; methods for reducing the severity of HIV infections; methods for reducing the severity of Ebola infections; methods for reducing the severity of influenza infections; methods for reducing the severity of RSV infections;

[0012] Methods for delaying the onset of disease; methods for delaying the onset of viral infection and / or post-viral syndrome; methods for delaying the onset of coronavirus infection and / or post-coronavirus syndrome; methods for delaying the onset of MERS-CoV infection; methods for delaying the onset of SARS-CoV infection; methods for delaying the onset of SARS-CoV-2 infection; methods for delaying the onset of HCoV-229E infection; methods for delaying the onset of HCoV-NL63 infection; methods for delaying the onset of HCoV-OC43 infection; methods for delaying the onset of HCoV-HKU1 infection; methods for delaying the onset of HIV infection; methods for delaying the onset of Ebola infection; methods for delaying the onset of influenza infection; methods for delaying the onset of RSV infection;

[0013] Methods for inhibiting the development of disease; methods for inhibiting viral entry into cells; methods for inhibiting coronavirus entry into cells; methods for inhibiting MERS-CoV viral entry into cells; methods for inhibiting SARS-CoV viral entry into cells; methods for inhibiting SARS-CoV-2 viral entry into cells; methods for inhibiting HCoV-229E viral entry into cells; methods for inhibiting HCoV-NL63 viral entry into cells; methods for inhibiting HCoV-OC43 viral entry into cells; methods for inhibiting HCoV-HKU1 viral entry into cells; methods for inhibiting HIV viral entry into cells; methods for inhibiting Ebola viral entry into cells; methods for inhibiting influenza viral entry into cells; methods for inhibiting RSV viral entry into cells;

[0014] Methods for modulating the interaction between one or more proteins; methods for modulating the interaction between a viral spike protein and a host cell membrane; methods for modulating the interaction between a coronavirus spike protein and a host cell membrane; methods for modulating the interaction between a MERS-CoV viral spike protein and a host cell membrane; methods for modulating the interaction between a SARS-CoV viral spike protein and a host cell membrane; methods for modulating the interaction between a SARS-CoV-2 spike protein and a host cell membrane; methods for modulating the interaction between a HCoV-229E spike protein and a host cell membrane a method for modulating the interaction between an HCoV-NL63 spike protein and a host cell membrane; a method for modulating the interaction between an HCoV-OC43 spike protein and a host cell membrane; a method for modulating the interaction between an HCoV-HKU1 spike protein and a host cell membrane; a method for modulating the interaction between an HIV spike protein and a host cell membrane; a method for modulating the interaction between an Ebola virus glycoprotein and a host cell membrane; a method for modulating the interaction between an influenza virus spike protein and a host cell membrane; a method for modulating the interaction between an RSV glycoprotein and a host cell membrane;

[0015] Methods for modulating the formation and translocation of protein complexes formed by one or more protein species; methods for modulating the formation and translocation of viral spike proteins to the cell surface of a subject and / or to the viral envelope; methods for modulating the formation and translocation of coronavirus spike proteins to the cell surface of a subject and / or to the viral envelope; methods for modulating the formation and translocation of MERS-CoV spike proteins to the cell surface of a subject and / or to the viral envelope; methods for modulating the formation and translocation of SARS-CoV spike proteins to the cell surface of a subject and / or to the viral envelope; methods for modulating the formation and translocation of SARS-CoV-2 spike proteins to the cell surface of a subject and / or to the viral envelope; methods for modulating the formation and translocation of HCoV-229E spike proteins to the cell surface of a subject and / or to the viral envelope; HC A method for modulating the formation and translocation of oV-NL63 spike protein to the cell surface of a subject and / or to the viral envelope; a method for modulating the formation and translocation of HCoV-OC43 spike protein to the cell surface of a subject and / or to the viral envelope; a method for modulating the formation and translocation of HCoV-HKU1 spike protein to the cell surface of a subject and / or to the viral envelope; a method for modulating the formation and translocation of HIV spike protein to the cell surface of a subject and / or to the viral envelope; a method for modulating the formation and translocation of Ebola virus glycoprotein to the cell surface of a subject and / or to the viral envelope; a method for modulating the formation and translocation of influenza virus spike protein to the cell surface of a subject and / or to the viral envelope; a method for modulating the formation and translocation of RSV glycoprotein to the cell surface of a subject and / or to the viral envelope;

[0016] A method for reducing the amount of a protein complex formed by one or more protein species in a subject's cells and / or on the cell surface; a method for reducing the amount of viral spike protein in a subject's cell surface and / or on the surface of the viral envelope; a method for reducing the amount of coronavirus spike protein in a subject's cell surface and / or on the surface of the viral envelope; a method for reducing the amount of MERS-CoV spike protein in a subject's cell surface and / or on the surface of the viral envelope; a method for reducing the amount of SARS-CoV spike protein in a subject's cell surface and / or on the surface of the viral envelope; a method for reducing the amount of SARS-CoV-2 spike protein in a subject's cell surface and / or on the surface of the viral envelope; a method for reducing the amount of HCoV-229E spike protein in a subject's cell surface and / or on the surface of the viral envelope. a method for reducing the amount of HCoV-NL63 spike protein on the cell surface of a subject and / or on the surface of the viral envelope; a method for reducing the amount of HCoV-OC43 spike protein on the cell surface of a subject and / or on the surface of the viral envelope; a method for reducing the amount of HCoV-HKU1 spike protein on the cell surface of a subject and / or on the surface of the viral envelope; a method for reducing the amount of HIV spike protein on the cell surface of a subject and / or on the surface of the viral envelope; a method for reducing the amount of Ebola virus glycoprotein on the cell surface of a subject and / or on the surface of the viral envelope; a method for reducing the amount of influenza virus spike protein on the cell surface of a subject and / or on the surface of the viral envelope; a method for reducing the amount of RSV glycoprotein on the cell surface of a subject and / or on the surface of the viral envelope;

[0017] Methods for promoting cellular proteasomal degradation of non-native protein complexes formed by one or more protein species; methods for promoting cellular proteasomal degradation of viral spike proteins; methods for promoting cellular proteasomal degradation of coronavirus spike proteins; methods for promoting cellular proteasomal degradation of MERS-CoV spike proteins; methods for promoting cellular proteasomal degradation of SARS-CoV spike proteins; methods for promoting cellular proteasomal degradation of SARS-CoV-2 spike proteins; methods for promoting cellular proteasomal degradation of HCoV-229E spike proteins a method for promoting cellular proteasomal degradation of HCoV-NL63 spike protein; a method for promoting cellular proteasomal degradation of HCoV-OC43 spike protein; a method for promoting cellular proteasomal degradation of HCoV-HKU1 spike protein; a method for promoting cellular proteasomal degradation of HIV spike protein; a method for promoting cellular proteasomal degradation of Ebola virus glycoprotein; a method for promoting cellular proteasomal degradation of influenza virus spike protein; a method for promoting cellular proteasomal degradation of RSV glycoprotein;

[0018] Nucleic acids; vectors; cells; pharmaceutical compositions; and kits. Because the SARS-CoV-2 virus causes COVID-19, any of the embodiments discussed in the context of SARS-CoV-2 can be implemented with respect to COVID-19.

[0019] Various methods of the disclosure can include one, two, three, four, five, six, or more of the following steps: administering a polypeptide to a subject; administering a nucleic acid to a subject; administering a vector to a subject; administering an antiviral agent to a subject;

[0020] diagnosing a subject as having a disease; diagnosing a subject as having a viral infection and / or post-viral syndrome; diagnosing a subject as having a coronavirus infection and / or post-coronavirus syndrome; diagnosing a subject as having a MERS-CoV infection; diagnosing a subject as having a SARS-CoV infection; diagnosing a subject as having a SARS-CoV-2 infection; diagnosing a subject as having an HCoV-229E infection; diagnosing a subject as having an HCoV-NL63 infection; diagnosing a subject as having an HCoV-OC43 infection; diagnosing a subject as having an HCoV-HKU1 infection; diagnosing a subject as having an HIV infection; diagnosing a subject as having an Ebola infection; diagnosing a subject as having an influenza infection; diagnosing a subject as having an RSV infection;

[0021] diagnosing a subject as having symptoms of a disease; diagnosing a subject as having symptoms of a viral infection and / or post-viral syndrome; diagnosing a subject as having symptoms of a coronavirus infection and / or post-coronavirus syndrome; diagnosing a subject as having symptoms of a MERS-CoV infection; diagnosing a subject as having symptoms of a SARS-CoV infection; diagnosing a subject as having symptoms of a SARS-CoV-2 infection; diagnosing a subject as having symptoms of an HCoV-229E infection; diagnosing a subject as having symptoms of an HCoV-NL63 infection; diagnosing a subject as having symptoms of an HCoV-OC43 infection; diagnosing a subject as having symptoms of an HCoV-HKU1 infection; diagnosing a subject as having symptoms of an HIV infection; diagnosing a subject as having symptoms of an Ebola infection; diagnosing a subject as having symptoms of an influenza infection; diagnosing a subject as having symptoms of an RSV infection;

[0022] diagnosing a subject as being at risk of having a disease; diagnosing a subject as being at risk of having a viral infection and / or post-viral syndrome; diagnosing a subject as being at risk of having a coronavirus infection and / or post-coronavirus syndrome; diagnosing a subject as being at risk of having a MERS-CoV infection; diagnosing a subject as being at risk of having a SARS-CoV infection; diagnosing a subject as being at risk of having a SARS-CoV-2 infection; diagnosing a subject as being at risk of having an HCoV-229E infection; diagnosing a subject as being at risk of having an HCoV-NL63 infection; diagnosing a subject as being at risk of having an HCoV-OC43 infection; diagnosing a subject as being at risk of having an HCoV-HKU1 infection; diagnosing a subject as being at risk of having an HIV infection; diagnosing a subject as being at risk of having an Ebola infection; diagnosing a subject as being at risk of having an influenza infection; diagnosing a subject as being at risk of having an RSV infection;

[0023] administering a second treatment for the disease to the subject; obtaining a sample from the subject; detecting a virus in the sample; detecting a coronavirus in the sample; detecting a MERS-CoV virus in the sample; detecting a SARS-CoV virus in the sample; detecting a SARS-CoV-2 virus in the sample; detecting an HCoV-229E virus in the sample; detecting an HCoV-NL63 virus in the sample; detecting an HCoV-OC43 virus in the sample; detecting an HCoV-HKU1 virus in the sample; detecting an HIV virus in the sample; detecting an Ebola virus in the sample; detecting an influenza virus in the sample; detecting RSV in the sample;

[0024] administering to the subject a second treatment for a viral infection and / or post-viral syndrome; administering to the subject a second treatment for a coronavirus infection and / or post-coronavirus syndrome; administering to the subject a second treatment for a MERS-CoV infection; administering to the subject a second therapy for a SARS-CoV infection; administering to the subject a second treatment for a SARS-CoV-2 infection; administering to the subject a second treatment for an HCoV-229E infection; administering to the subject a second treatment for an HCoV-NL63 infection; administering to the subject a second treatment for an HCoV-OC43 infection; administering to the subject a second treatment for an HCoV-HKU1 infection; administering to the subject a second treatment for an HIV infection; administering to the subject a second treatment for an Ebola infection; administering to the subject a second treatment for an influenza infection; administering to the subject a second treatment for a RSV infection; administering to the subject three or more types of antiviral therapy. Certain embodiments of the present disclosure may exclude one or more of the foregoing elements and / or steps.

[0025] Various compositions of the present disclosure can include at least one, two, three, four, five, or more of the following components: polypeptides, proteins, nucleic acids, vectors, therapeutic agents, antiviral agents, pharmaceutically acceptable carriers, and excipients, one or more of which may be specifically excluded from certain embodiments.

[0026] Disclosed herein, in some embodiments, is a method for modulating a target protein or its biological function in vivo in a subject, comprising contacting the target protein or a portion thereof and / or a native interaction partner of the target protein or a portion thereof with an effective amount of a polypeptide having an amino acid sequence corresponding to that of the target protein, wherein the polypeptide is more than 30 amino acids in length, and wherein the polypeptide and the target protein form a non-native protein complex when the target protein contacts the polypeptide, thereby modulating the target protein or its biological function in vivo; the polypeptide and the native interaction partner of the target protein form a non-native protein complex when the native interaction partner of the target protein contacts the polypeptide, thereby modulating the target protein or its biological function in vivo; and / or the polypeptide, the target protein, and the native interaction partner of the target protein form a non-native protein complex when the target protein and the native interaction partner of the target protein contact the polypeptide, thereby modulating the target protein or its biological function in vivo.

[0027] In some embodiments, a polypeptide having an amino acid sequence corresponding to a target protein sequence has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the target protein sequence. In some embodiments, a polypeptide having an amino acid sequence corresponding to a target protein sequence has at least 10% sequence identity to the target protein sequence. In some embodiments, a polypeptide having an amino acid sequence corresponding to a target protein sequence has at least 20% identity to the target protein sequence. In some embodiments, a polypeptide having an amino acid sequence corresponding to a target protein sequence has at least 30% identity to the target protein sequence. In some embodiments, a polypeptide having an amino acid sequence corresponding to a target protein sequence is at least 40% identical to the target protein sequence. In some embodiments, a polypeptide having an amino acid sequence corresponding to a target protein sequence is at least 50% identical to the target protein sequence. In some embodiments, a polypeptide having an amino acid sequence corresponding to a target protein sequence is at least 60% identical to the target protein sequence. In some embodiments, a polypeptide having an amino acid sequence corresponding to a target protein sequence is at least 70% identical to the target protein sequence. In some embodiments, a polypeptide having an amino acid sequence corresponding to a target protein sequence is at least 80% identical to the target protein sequence. In some embodiments, a polypeptide having an amino acid sequence corresponding to a target protein sequence is at least 85% identical to the target protein sequence. In some embodiments, a polypeptide having an amino acid sequence corresponding to a target protein sequence is at least 90% identical to the target protein sequence.In some embodiments, a polypeptide having an amino acid sequence corresponding to the sequence of a target protein has at least 95% identity to the sequence of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to the sequence of a target protein comprises the corresponding sequence of the target protein.

[0028] Disclosed herein, in some embodiments, is a method for modulating a target protein or its biological function in vivo in a subject, comprising contacting the target protein or a portion thereof and / or a native interaction partner of the target protein or a portion thereof with an effective amount of a polypeptide having an amino acid sequence corresponding to an oligomerization domain of the target protein, wherein the polypeptide is more than 30 amino acids in length, and wherein the polypeptide oligomerizes with the oligomerization domain of the target protein to form a non-native protein complex, thereby modulating the target protein or its biological function in vivo; the polypeptide oligomerizes with the oligomerization domain of the target protein's native interaction partner to form a non-native protein complex, thereby modulating the target protein or its biological function in vivo; and / or the polypeptide oligomerizes with the oligomerization domain of the target protein and the target protein's native interaction partner to form a non-native protein complex, thereby modulating the target protein or its biological function in vivo.

[0029] In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the oligomerization domain of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein has at least 10% sequence identity to the oligomerization domain of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein has at least 20% identity to the oligomerization domain of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein has at least 30% identity to the oligomerization domain of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein has at least 40% identity to the oligomerization domain of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein has at least 50% identity to the oligomerization domain of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein has at least 60% identity to the oligomerization domain of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein has at least 70% identity to the oligomerization domain of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein has at least 80% identity to the oligomerization domain of the target protein.In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein is at least 85% identical to the oligomerization domain of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein is at least 90% identical to the oligomerization domain of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein is at least 95% identical to the oligomerization domain of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein comprises the oligomerization domain of the target protein.

[0030] In some embodiments, the target protein is a viral protein. In some embodiments, the target protein is a viral glycoprotein. In some embodiments, the target protein is a viral spike protein. In some embodiments, modulating the target protein or its biological function in vivo treats or prevents a disease or condition in a subject. In some embodiments, the disease or condition is a viral infection.

[0031] In some embodiments, the non-native protein complex undergoes proteasomal degradation. In some embodiments, the formation of the non-native protein complex inhibits the target protein or its biological function in vivo by inhibiting homo-oligomerization of the target protein. In some embodiments, the formation of the non-native protein complex inhibits the target protein or its biological function in vivo by inhibiting hetero-oligomerization of the target protein. In some embodiments, the formation of the non-native protein complex inhibits the target protein or its biological function in vivo by inhibiting homo- and hetero-oligomerization of the target protein.

[0032] Disclosed herein, in some embodiments, are the following methods:

[0033] A method for modulating a coronavirus spike protein or a biological function thereof in vivo in a subject, the method comprising contacting the coronavirus spike protein or a portion thereof with an effective amount of a polypeptide comprising an amino acid sequence having at least 10% identity to SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16;

[0034] A method for modulating coronavirus spike protein or a biological function thereof in vivo in a subject, comprising contacting coronavirus spike protein or a portion thereof with an effective amount of a polypeptide having an amino acid sequence corresponding to an oligomerization domain of the coronavirus spike protein and having at least 10% identity to SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16, wherein the polypeptide oligomerizes with the oligomerization domain of the coronavirus spike protein to form a non-native protein complex, thereby modulating coronavirus spike protein or a biological function thereof in vivo;

[0035] A method for treating or preventing a coronavirus infection in a subject, the method comprising administering to the subject a therapeutically effective amount of a composition comprising a polypeptide comprising an amino acid sequence having at least 10% identity to SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16; and

[0036] A method for treating or preventing a coronavirus infection in a subject, comprising administering to the subject a therapeutically effective amount of a composition comprising a polypeptide having an amino acid sequence corresponding to the oligomerization domain of the coronavirus spike protein and having at least 10% identity to SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14 or SEQ ID NO:16, wherein the polypeptide oligomerizes with the oligomerization domain of the coronavirus spike protein to form a non-native protein complex.

[0037] In some embodiments, the non-native protein complex undergoes proteasomal degradation. In some embodiments, modulating the coronavirus spike protein or its biological function in vivo treats or prevents coronavirus infection in a subject. In some embodiments, modulating the coronavirus spike protein or its biological function in vivo comprises inhibiting the formation and translocation of the coronavirus spike protein to the cell surface and / or to the viral envelope of the subject. In some embodiments, modulating the coronavirus spike protein or its biological function in vivo reduces the amount of coronavirus spike protein on the cell surface of the subject and / or on the surface of the viral envelope. In some embodiments, oligomerization of a polypeptide with the coronavirus spike protein modulates the coronavirus spike protein or its biological function to treat or prevent coronavirus infection. In some embodiments, the formation and translocation of the coronavirus spike protein to the cell surface and / or to the viral envelope of the subject is inhibited. In some embodiments, the amount of coronavirus spike protein on the cell surface of the subject and / or on the surface of the viral envelope is reduced.

[0038] In some embodiments, the coronavirus comprises SARS-CoV, SARS-CoV-2, MERS-CoV, HCoV-229E, HCoV-NL63, HCoV-OC43, or HCoV-HKU1. In some embodiments, the coronavirus comprises SARS-CoV, and the coronavirus spike protein comprises a SARS-CoV spike protein. In some embodiments, the coronavirus comprises SARS-CoV-2, and the coronavirus spike protein comprises a SARS-CoV-2 spike protein. In some embodiments, the coronavirus comprises MERS-CoV, and the coronavirus spike protein comprises a MERS-CoV spike protein. In some embodiments, the coronavirus comprises HCoV-229E, and the coronavirus spike protein comprises an HCoV-229E spike protein. In some embodiments, the coronavirus comprises HCoV-NL63, and the coronavirus spike protein comprises an HCoV-NL63 spike protein. In some embodiments, the coronavirus comprises HCoV-OC43, and the coronavirus spike protein comprises an HCoV-OC43 spike protein. In some embodiments, the coronavirus comprises HCoV-HKU1 and the coronavirus spike protein comprises an HCoV-HKU1 spike protein.

[0039] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:2. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO:2. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO:2. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO:2. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO:2. In some embodiments, the polypeptide comprises SEQ ID NO:2.

[0040] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:4. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO:4. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO:4. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO:4. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO:4. In some embodiments, the polypeptide comprises SEQ ID NO:4.

[0041] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:6. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO:6. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO:6. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO:6. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO:6. In some embodiments, the polypeptide comprises SEQ ID NO:6.

[0042] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 8. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO: 8. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO: 8. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO: 8. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO: 8. In some embodiments, the polypeptide comprises SEQ ID NO: 8.

[0043] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 10. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO: 10. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO: 10. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO: 10. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO: 10. In some embodiments, the polypeptide comprises SEQ ID NO: 10.

[0044] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 12. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO: 12. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO: 12. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO: 12. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO: 12. In some embodiments, the polypeptide comprises SEQ ID NO: 12.

[0045] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 14. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO: 14. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO: 14. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO: 14. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO: 14. In some embodiments, the polypeptide comprises SEQ ID NO: 14.

[0046] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 16. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO: 16. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO: 16. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO: 16. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO: 16. In some embodiments, the polypeptide comprises SEQ ID NO: 16.

[0047] In some embodiments, the methods for modulating a coronavirus spike protein or its biological function in vivo and / or methods for treating or preventing a coronavirus infection further include diagnosing the subject with a coronavirus infection; diagnosing the subject as having symptoms of a coronavirus infection; or diagnosing the subject as at risk for having a coronavirus infection. In some embodiments, the subject is at high risk for having a coronavirus infection. In some embodiments, the subject does not have a coronavirus infection. In some embodiments, the subject tests negative for a coronavirus infection. In some embodiments, the subject has been diagnosed with a coronavirus infection. In some embodiments, the coronavirus infection causes severe acute respiratory syndrome (SARS), Middle East respiratory syndrome, or a respiratory infection. In some embodiments, the coronavirus infection causes COVID-19. In some embodiments, the coronavirus infection is prevented, reduced in severity, and / or delayed in onset.

[0048] In some embodiments, the subject is administered an effective amount of a second treatment for coronavirus infection. In some embodiments, the second treatment comprises an antibiotic, an antiviral, convalescent serum, an immunomodulator, an anticoagulant, a body fluid, oxygen, a corticosteroid, an antibody, GSnP-6, a sialyl Lewis X analog, an antiproliferative agent, a calcineurin inhibitor, an anti-signaling compound, or a combination thereof. In some embodiments, the second treatment comprises an anti-SARS-CoV-2 drug.In some embodiments, the anti-SARS-CoV-2 drug is a steroid, zinc, vitamin C, remdesivir, tocilizumab, anakinra, beclomethasone, betamethasone, budesonide cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisolone, prednisone, triamcinolone, azithromycin, AC-55541, Apicidin, AZ3451, AZ8838, bafilomycin A1, CCT 365623, Daunorubicin, E-52862, Entacapone, GB110, H-89, Haloperidol, Indomethacin, JQ1, Loratadine, Merimepodib, Metformin, Midostaurin, Migalastat, Mycophenolic Acid, PB28, PD-144418, Ponatinib, Ribavirin, RS-PPCC, Ruxolitinib, RVX-208, S-Verapamil, Silmitasertib, TMCB, UCPH-101, Valproic Acid, XL413, ZINC1775962367, ZINC4326719, ZINC4511851, ZINC95559591, 4E2RCat, ABBV-744, Camostat, Captopril, CB50 83, chloramphenicol, chloroquine, hydroxychloroquine, CPI-0610, dabrafenib, DBeQ, dBET6, IHVR-19029, linezolid, lisinopril, minoxidil, ML240, MZ1, nafamostat, pevonedistat, PS3061, rapamycin (sirolimus), sanglifehrin A, sapanisertib (INK128 / MlN128), FK-506 (tacrolimus), Ternatin 4 (DA3), tigecycline, tomivosertib (eFT-508), veldinexor, WDB002, zotatifine (eFT226), and combinations thereof.

[0049] Disclosed herein, in some embodiments, are the following methods:

[0050] A method for modulating an HIV spike protein or a biological function thereof in vivo in a subject, the method comprising contacting the HIV spike protein or a portion thereof with an effective amount of a polypeptide comprising an amino acid sequence having at least 10% identity to SEQ ID NO: 18;

[0051] A method for modulating HIV spike protein or a biological function thereof in vivo in a subject, comprising contacting the HIV spike protein or a portion thereof with an effective amount of a polypeptide having an amino acid sequence corresponding to the oligomerization domain of the HIV spike protein and having at least 10% identity to SEQ ID NO: 18, wherein the polypeptide oligomerizes with the oligomerization domain of the HIV spike protein to form a non-native protein complex, thereby modulating the HIV spike protein or a biological function thereof in vivo;

[0052] A method for treating or preventing HIV infection in a subject, the method comprising administering to the subject a therapeutically effective amount of a composition comprising a polypeptide comprising an amino acid sequence having at least 10% identity to SEQ ID NO: 18; and

[0053] A method for treating or preventing HIV infection in a subject, comprising administering to the subject a therapeutically effective amount of a composition comprising a polypeptide having an amino acid sequence corresponding to the oligomerization domain of the HIV spike protein and having at least 10% identity to SEQ ID NO: 18, wherein the polypeptide oligomerizes with the oligomerization domain of the HIV spike protein to form a non-native protein complex.

[0054] In some embodiments, the non-native protein complex undergoes proteasomal degradation. In some embodiments, HIV infection is treated or prevented in a subject by modulating the HIV spike protein or its biological function in vivo. In some embodiments, modulating the HIV spike protein or its biological function in vivo comprises inhibiting the formation and translocation of the HIV spike protein to the cell surface and / or to the viral envelope of the subject. In some embodiments, modulating the HIV spike protein or its biological function in vivo reduces the amount of HIV spike protein on the cell surface of the subject and / or on the surface of the viral envelope. In some embodiments, oligomerization of a polypeptide with the HIV spike protein modulates the HIV spike protein or its biological function to treat or prevent HIV infection. In some embodiments, the formation and translocation of the HIV spike protein to the cell surface and / or to the viral envelope of the subject is inhibited. In some embodiments, the amount of HIV spike protein on the cell surface of the subject and / or on the surface of the viral envelope is reduced.

[0055] In some embodiments, the HIV spike protein comprises the gp160 spike protein of HIV.

[0056] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 18. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO: 18. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO: 18. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO: 18. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO: 18. In some embodiments, the polypeptide comprises SEQ ID NO: 18.

[0057] In some embodiments, the method for modulating HIV spike protein or its biological function in vivo and / or the method for treating or preventing HIV infection further comprises diagnosing the subject with HIV infection; diagnosing the subject as having symptoms of HIV infection; or diagnosing the subject as at risk for having HIV infection. In some embodiments, the subject is at high risk for having HIV infection. In some embodiments, the subject does not have HIV infection. In some embodiments, the subject has tested negative for HIV infection. In some embodiments, the subject has been diagnosed with HIV infection. In some embodiments, HIV infection is prevented, reduced in severity, and / or delayed in onset.

[0058] In some embodiments, the subject is administered an effective amount of a second treatment for HIV infection. In some embodiments, the second treatment comprises an antibiotic, an antiviral, convalescent serum, an immunomodulator, an anticoagulant, a body fluid, oxygen, a corticosteroid, an antibody, GSnP-6, a sialyl Lewis X analog, an antiproliferative agent, a calcineurin inhibitor, an anti-signaling compound, or a combination thereof. In some embodiments, the second treatment comprises an anti-HIV drug. In some embodiments, the anti-HIV drug is efavirenz (Sustiva), rilpivirine (Edurant), etravirine (Intelence), delavirdine (Rescriptor), nevirapine (Viramune, Viramune) XR), doravirine (Pifeltroz), abacavir (Ziagen), tenofovir alafenamide fumarate (Vemlidy), tenofovir (Viread), emtricitabine (Emtriva), lamivudine (Epivir), zidovudine (Retrovir), abacavir / lamivudine / zidovudine (Trizivir), abacavir / lamivudine (Epzicom), emtricitabine / tenofovir (Truvada), abacavir / lamivudine (Epzicom), lamivudine / tenofovir disoproxil fumarate (Cimduo, Temixys), lamivudine / zidovudine (Combivir), emtricitabine / tenofovir alafenamide (Descovy), didanosine (Videx, Videx) EC), stavudine (Zerit), atazanavir (Reyataz), darunavir (Prezista), fosamprenavir (Lexiva), ritonavir (Norvir), tipranavir (Aptivus), lopinavir / ritonavir (Kaletra), atazanavir / cobicistat (Evotaz), darunavir / cobicistat (Prezcobix), indinavir (Crixivan), nelfinavir (Viracept), saquinavir (Invirase), bictegravir sodium / emtricitabine / tenofovir alafenamidefumar) (Biktarvy), raltegravir (Isentress), elvitegravir (Genvoya and Stribild), dolutegravir (Tivicay), cobicistat (Tybost), ritonavir (Norvir), enfuvirtide (Fuzeon), maraviroc (Selzentry), ibalizumab-uiyk (Trogarzo), maraviroc (Selzentry), fostemsavir (Rukobia), doravirine / lamivudine / tenofovir disoproxil fumarate (Delstrigo), efavirenz / lamivudine / tenofovir disoproxil fumarate (Symfi), efavirenz / lamivudine / tenofovir disoproxil fumarate (Symfi) Lo), efavirenz / emtricitabine / tenofovir disoproxil fumarate (Atripla), emtricitabine / rilpivirine / tenofovir alafenamide fumarate (Odefsey), emtricitabine / rilpivirine / tenofovir disoproxil fumarate (Complera), elvitegravir / cobicistat / emtricitabine / tenofovir disoproxil fumarate (Stribild), elvitegravir / cobicistat / emtricitabine / tenofovir alafenamide fumarate (Genvoya), abacavir / dolutegravir / rilpivir ... Selected from the group consisting of mivudine (Triumeq), bictegravir / emtricitabine / tenofovir alafenamide fumarate (Biktarvy), dolutegravir / lamivudine (Dovato), dolutegravir / rilpivirine (Juluca), darunavir / cobicistat / emtricitabine / tenofovir alafenamide fumarate (Symtuza), acetyl-L-carnitine, whey protein, L-glutamine, L-arginine, hydroxymethylbutyrate (HMB), probiotics, vitamins and minerals, and combinations thereof.

[0059] Disclosed herein, in some embodiments, are the following methods:

[0060] 1. A method for modulating an Ebola glycoprotein or a biological function thereof in vivo in a subject, the method comprising contacting the Ebola glycoprotein or a portion thereof with an effective amount of a polypeptide comprising an amino acid sequence having at least 10% identity to SEQ ID NO: 20;

[0061] a method for modulating the Ebola glycoprotein or its biological function in vivo in a subject, the method comprising contacting the Ebola glycoprotein or a portion thereof with an effective amount of a polypeptide having an amino acid sequence corresponding to the oligomerization domain of the Ebola glycoprotein and having at least 10% identity to SEQ ID NO: 20, wherein the polypeptide oligomerizes with the oligomerization domain of the Ebola glycoprotein to form a non-native protein complex, thereby inhibiting the Ebola glycoprotein or its biological function in vivo;

[0062] A method for treating or preventing an Ebola infection in a subject, the method comprising administering to the subject a therapeutically effective amount of a composition comprising a polypeptide comprising an amino acid sequence having at least 10% identity to SEQ ID NO: 20; and

[0063] 1. A method for treating or preventing an Ebola infection in a subject, comprising administering to the subject a therapeutically effective amount of a composition comprising a polypeptide having an amino acid sequence corresponding to the oligomerization domain of the Ebola glycoprotein and having at least 10% identity to SEQ ID NO: 20, wherein the polypeptide oligomerizes with the oligomerization domain of the Ebola glycoprotein to form a non-native protein complex.

[0064] In some embodiments, the non-native protein complex undergoes proteasomal degradation. In some embodiments, modulating the Ebola glycoprotein or its biological function in vivo treats or prevents Ebola infection in a subject. In some embodiments, modulating the Ebola glycoprotein or its biological function in vivo comprises inhibiting the formation and translocation of the Ebola glycoprotein to the cell surface of the subject and / or to the viral envelope. In some embodiments, modulating the Ebola glycoprotein or its biological function in vivo reduces the amount of Ebola glycoprotein on the cell surface of the subject and / or on the surface of the viral envelope. In some embodiments, oligomerization of a polypeptide with the Ebola glycoprotein modulates the Ebola glycoprotein or its biological function to treat or prevent Ebola infection. In some embodiments, the formation and translocation of the Ebola glycoprotein to the cell surface of the subject and / or to the viral envelope is inhibited. In some embodiments, the amount of Ebola glycoprotein on the cell surface of the subject and / or on the surface of the viral envelope is reduced. In some embodiments, Ebola infection is prevented, reduced in severity, and / or delayed in onset.

[0065] In some embodiments, the Ebola glycoprotein comprises the Ebola GP glycoprotein.

[0066] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 20. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO: 20. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO: 20. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO: 20. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO: 20. In some embodiments, the polypeptide comprises SEQ ID NO: 20.

[0067] In some embodiments, the methods for modulating the Ebola glycoprotein or its biological function in vivo and / or methods for treating or preventing an Ebola infection further comprise diagnosing the subject with an Ebola infection; diagnosing the subject as having symptoms of an Ebola infection; or diagnosing the subject as at risk for having an Ebola infection. In some embodiments, the subject is at high risk for having an Ebola infection. In some embodiments, the subject does not have an Ebola infection. In some embodiments, the subject has tested negative for an Ebola infection. In some embodiments, the subject has been diagnosed with an Ebola infection.

[0068] In some embodiments, the subject is administered an effective amount of a second treatment for Ebola infection. In some embodiments, the second treatment comprises an antibiotic, an antiviral, convalescent serum, an immunomodulator, an anticoagulant, a body fluid, oxygen, a corticosteroid, an antibody, GSnP-6, a sialyl Lewis X analog, an antiproliferative agent, a calcineurin inhibitor, an anti-signaling compound, or a combination thereof. In some embodiments, the second treatment comprises an anti-Ebola drug. In some embodiments, the anti-Ebola drug is selected from the group consisting of atoltivimab / maftivimab / odesivimab-ebgn (Inmazeb), ansuvimab-zykl (Ebanga), favipiravir (Avigan), ribavirin, BCX4430, brincidofovir, TKM-Ebola, AVI-7537, JK-05, and combinations thereof.

[0069] Disclosed herein, in some embodiments, are the following methods:

[0070] A method for modulating influenza virus spike protein or a biological function thereof in vivo in a subject, the method comprising contacting the influenza virus spike protein or a portion thereof with an effective amount of a polypeptide comprising an amino acid sequence having at least 10% identity to SEQ ID NO: 25;

[0071] A method for modulating influenza virus spike protein or a biological function thereof in vivo in a subject, comprising contacting influenza virus spike protein or a portion thereof with an effective amount of a polypeptide having an amino acid sequence corresponding to an oligomerization domain of the influenza virus spike protein and having at least 10% identity to SEQ ID NO: 25, wherein the polypeptide oligomerizes with the oligomerization domain of the influenza virus spike protein to form a non-native protein complex, thereby modulating influenza virus spike protein or a biological function thereof in vivo;

[0072] A method for treating or preventing an influenza infection in a subject, the method comprising administering to the subject a therapeutically effective amount of a composition comprising a polypeptide comprising an amino acid sequence having at least 10% identity to SEQ ID NO: 25; and

[0073] A method for treating or preventing influenza infection in a subject, comprising administering to the subject a therapeutically effective amount of a composition comprising a polypeptide having an amino acid sequence corresponding to the oligomerization domain of an influenza virus spike protein and having at least 10% identity to SEQ ID NO: 25, wherein the polypeptide oligomerizes with the oligomerization domain of the influenza virus spike protein to form a non-native protein complex.

[0074] In some embodiments, the non-native protein complex undergoes proteasomal degradation. In some embodiments, modulating an influenza virus spike protein or its biological function in vivo treats or prevents influenza infection in a subject. In some embodiments, modulating an influenza virus spike protein or its biological function in vivo comprises inhibiting the formation and translocation of influenza virus spike protein to the cell surface of a subject and / or to the viral envelope. In some embodiments, modulating an influenza virus spike protein or its biological function in vivo reduces the amount of influenza virus spike protein on the cell surface of a subject and / or on the surface of the viral envelope. In some embodiments, oligomerization of a polypeptide with an influenza virus spike protein modulates the influenza virus spike protein or its biological function to treat or prevent influenza infection. In some embodiments, the formation and translocation of influenza virus spike protein to the cell surface of a subject and / or to the viral envelope is inhibited. In some embodiments, the amount of influenza virus spike protein on the cell surface of a subject and / or on the surface of the viral envelope is reduced.

[0075] In some embodiments, the influenza comprises an influenza A virus, and the influenza virus spike protein comprises an influenza A virus spike protein. In some embodiments, the influenza A virus comprises an influenza A / H1 virus, and the influenza virus spike protein comprises an influenza A / H1 virus HA spike protein. In some embodiments, the influenza A virus comprises an influenza A / H3 virus, and the influenza virus spike protein comprises an influenza A / H3 virus HA spike protein. In some embodiments, the influenza comprises an influenza B virus, and the influenza virus spike protein comprises an influenza B virus spike protein. In some embodiments, the influenza B virus comprises an influenza B / Victoria virus, and the influenza virus spike protein comprises an influenza B / Victoria virus HA spike protein. In some embodiments, the influenza B virus comprises an influenza B / Yamagata virus, and the influenza virus spike protein comprises an influenza B / Yamagata virus HA spike protein.

[0076] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 25. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO: 25. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO: 25. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO: 25. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO: 25. In some embodiments, the polypeptide comprises SEQ ID NO: 25.

[0077] In some embodiments, the method for modulating an influenza virus spike protein or its biological function in vivo and / or the method for treating or preventing an influenza virus infection further comprises diagnosing the subject with an influenza infection; diagnosing the subject as having symptoms of an influenza infection; or diagnosing the subject as at risk for having an influenza infection. In some embodiments, the subject is at high risk for having an influenza infection. In some embodiments, the subject does not have an influenza infection. In some embodiments, the subject tests negative for an influenza infection. In some embodiments, the subject has been diagnosed with an influenza infection. In some embodiments, the influenza infection is prevented, reduced in severity, and / or delayed in onset.

[0078] In some embodiments, the subject is administered an effective amount of a second treatment for influenza infection. In some embodiments, the second treatment comprises an antibiotic, an antiviral, a convalescent serum, an immunomodulator, an anticoagulant, a body fluid, oxygen, a corticosteroid, an antibody, GSnP-6, a sialyl Lewis X analog, an antiproliferative agent, a calcineurin inhibitor, an anti-signaling compound, or a combination thereof. In some embodiments, the second treatment comprises an anti-influenza drug. In some embodiments, the anti-influenza drug is selected from the group consisting of oseltamivir phosphate (Tamiflu), zanamivir (Relenza), peramivir (Rapivab), baloxavir marboxil (Xofluza), amantadine, rimantadine (Flumadine), umifenovir (Arbidol), moroxydine, fluticare, acetaminophen, chlorpheniramine, dextromethorphan, pseudoephedrine, and combinations thereof.

[0079] Disclosed herein, in some embodiments, are the following methods:

[0080] A method for modulating an RSV glycoprotein or a biological function thereof in vivo in a subject, comprising contacting the RSV glycoprotein or a portion thereof with an effective amount of a polypeptide comprising an amino acid sequence having at least 10% identity to SEQ ID NO: 34;

[0081] A method for modulating a RSV glycoprotein or a biological function thereof in vivo in a subject, comprising contacting a RSV glycoprotein or a portion thereof with an effective amount of a polypeptide having an amino acid sequence corresponding to an oligomerization domain of the RSV glycoprotein and having at least 10% identity to SEQ ID NO: 34, wherein the polypeptide oligomerizes with the oligomerization domain of the RSV glycoprotein to form a non-native protein complex, thereby inhibiting the RSV glycoprotein or a biological function thereof in vivo;

[0082] A method for treating or preventing a RSV infection in a subject, the method comprising administering to the subject a therapeutically effective amount of a composition comprising a polypeptide comprising an amino acid sequence having at least 10% identity to SEQ ID NO: 34; and

[0083] 1. A method for treating or preventing a RSV infection in a subject, comprising administering to the subject a therapeutically effective amount of a composition comprising a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a RSV glycoprotein and having at least 10% identity to SEQ ID NO: 34, wherein the polypeptide oligomerizes with the oligomerization domain of an Ebola glycoprotein to form a non-native protein complex.

[0084] In some embodiments, the non-native protein complex undergoes proteasomal degradation. In some embodiments, modulating the RSV glycoprotein or its biological function in vivo treats or prevents RSV infection in a subject. In some embodiments, modulating the RSV glycoprotein or its biological function in vivo includes inhibiting the formation and translocation of the RSV glycoprotein to the cell surface and / or viral envelope of a subject. In some embodiments, modulating the RSV glycoprotein or its biological function in vivo reduces the amount of the RSV glycoprotein on the cell surface of a subject and / or on the surface of the viral envelope. In some embodiments, oligomerization of a polypeptide with the RSV glycoprotein modulates the RSV glycoprotein or its biological function to treat or prevent RSV infection. In some embodiments, the formation and translocation of the RSV glycoprotein to the cell surface and / or viral envelope of a subject is inhibited. In some embodiments, the amount of RSV glycoprotein on the cell surface of a subject and / or on the surface of the viral envelope is reduced. In some embodiments, RSV infection is prevented, reduced in severity, and / or delayed in onset.

[0085] In some embodiments, the RSV glycoprotein comprises the F glycoprotein of RSV.

[0086] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 34. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO: 34. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO: 34. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO: 34. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO: 34. In some embodiments, the polypeptide comprises SEQ ID NO: 34.

[0087] In some embodiments, the method for regulating a RSV glycoprotein or its biological function in vivo and / or the method for treating or preventing a RSV infection further includes diagnosing the subject with a RSV infection; diagnosing the subject as having symptoms of a RSV infection; or diagnosing the subject as being at risk for a RSV infection. In some embodiments, the subject is at high risk for having a RSV infection. In some embodiments, the subject does not have a RSV infection. In some embodiments, the subject tests negative for a RSV infection. In some embodiments, the subject has been diagnosed with a RSV infection.

[0088] In some embodiments, the subject is administered an effective amount of a second treatment for the RSV infection, hi some embodiments, the second treatment comprises an anti-RSV drug.

[0089] In some embodiments of the methods disclosed herein, a dose of between 0.1 mg and 1000 mg of polypeptide per kg of subject body weight is administered to the subject. In some embodiments, a dose of between 0.1 μg and 1000 μg of polypeptide per kg of subject body weight is administered to the subject.

[0090] In some embodiments, the polypeptide is expressed from a vector encoding the polypeptide. In some embodiments, the vector is a viral vector or a non-viral vector. In some embodiments, the vector is a minicircle DNA vector. In some embodiments, the vector copies are greater than 1 x 10 per kg of subject body weight. 8 ~1×10 18 In some embodiments, the subject is administered a dose that is between about 1 x 10 vector copies per kg of the subject's body weight. 11 ~Approx. 1×10 14 In some embodiments, the vector is administered to the subject at a dose of about 1 x 10 per kg of the subject's body weight. 12 ~Approx. 1×10 15 In some embodiments, the vector transduces cells of the subject such that the polypeptide is expressed by the cells of the subject.

[0091] In some embodiments, the composition further comprises a pharmaceutically acceptable carrier, hi some embodiments, the pharmaceutically acceptable carrier comprises a liposome, a polymeric micelle, a microsphere, or a nanoparticle.

[0092] In some embodiments, a single dose of the composition is administered. In some embodiments, multiple doses of the composition are administered. In some embodiments, the composition is delivered to the subject once daily, more than once daily, more than once weekly, more than once monthly, or more than once yearly. In some embodiments, the composition is delivered systemically or locally. In some embodiments, the composition is administered to the subject by intranasal administration, intravenous administration, intraperitoneal administration, intratracheal administration, intramuscular administration, endoscopic administration, transdermal administration, subcutaneous administration, topical administration, intracranial administration, inhalation, injection, infusion, or perfusion. In some embodiments, the composition is administered to the subject by inhalation. In some embodiments, the composition is administered to the subject by intranasal administration.

[0093] Disclosed herein, in some embodiments, is a pharmaceutical composition comprising a vector encoding a polypeptide having an amino acid sequence corresponding to the sequence of a target protein, wherein the polypeptide is more than 30 amino acids in length and the polypeptide has at least 10% sequence identity with the sequence of the target protein.

[0094] In some embodiments, a polypeptide having an amino acid sequence corresponding to a target protein sequence has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the target protein sequence. In some embodiments, a polypeptide having an amino acid sequence corresponding to a target protein sequence has at least 10% sequence identity to the target protein sequence. In some embodiments, a polypeptide having an amino acid sequence corresponding to a target protein sequence has at least 20% identity to the target protein sequence. In some embodiments, a polypeptide having an amino acid sequence corresponding to a target protein sequence has at least 30% identity to the target protein sequence. In some embodiments, a polypeptide having an amino acid sequence corresponding to a target protein sequence is at least 40% identical to the target protein sequence. In some embodiments, a polypeptide having an amino acid sequence corresponding to a target protein sequence is at least 50% identical to the target protein sequence. In some embodiments, a polypeptide having an amino acid sequence corresponding to a target protein sequence is at least 60% identical to the target protein sequence. In some embodiments, a polypeptide having an amino acid sequence corresponding to a target protein sequence is at least 70% identical to the target protein sequence. In some embodiments, a polypeptide having an amino acid sequence corresponding to a target protein sequence is at least 80% identical to the target protein sequence. In some embodiments, a polypeptide having an amino acid sequence corresponding to a target protein sequence is at least 85% identical to the target protein sequence. In some embodiments, a polypeptide having an amino acid sequence corresponding to a target protein sequence is at least 90% identical to the target protein sequence.In some embodiments, a polypeptide having an amino acid sequence corresponding to the sequence of a target protein has at least 95% identity to the sequence of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to the sequence of a target protein comprises the corresponding sequence of the target protein.

[0095] Disclosed herein, in some embodiments, is a pharmaceutical composition comprising a vector encoding a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein, wherein the polypeptide is greater than 30 amino acids in length and has at least 10% sequence identity with the oligomerization domain of the target protein.

[0096] In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the oligomerization domain of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein has at least 10% identity to the oligomerization domain of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein has at least 20% identity to the oligomerization domain of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein has at least 30% identity to the oligomerization domain of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein has at least 40% identity to the oligomerization domain of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein has at least 50% identity to the oligomerization domain of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein has at least 60% identity to the oligomerization domain of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein has at least 70% identity to the oligomerization domain of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein has at least 80% identity to the oligomerization domain of the target protein.In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein is at least 85% identical to the oligomerization domain of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein is at least 90% identical to the oligomerization domain of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein is at least 95% identical to the oligomerization domain of the target protein. In some embodiments, a polypeptide having an amino acid sequence corresponding to an oligomerization domain of a target protein comprises the oligomerization domain of the target protein.

[0097] In some embodiments, the target protein comprises a viral protein. In some embodiments, the target protein comprises a viral glycoprotein. In some embodiments, the target protein comprises a viral spike protein.

[0098] Disclosed herein, in some embodiments, are pharmaceutical compositions comprising a vector encoding a polypeptide comprising an amino acid sequence having at least 10% identity to SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16; and pharmaceutical compositions comprising a vector encoding a polypeptide corresponding to the oligomerization domain of a coronavirus spike protein and having an amino acid sequence having at least 10% identity to SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16.

[0099] In some embodiments, the coronavirus spike protein comprises a SARS-CoV spike protein. In some embodiments, the coronavirus spike protein comprises a SARS-CoV-2 spike protein. In some embodiments, the coronavirus spike protein comprises a MERS-CoV spike protein. In some embodiments, the coronavirus spike protein comprises an HCoV-229E spike protein. In some embodiments, the coronavirus spike protein comprises an HCoV-NL63 spike protein. In some embodiments, the coronavirus spike protein comprises an HCoV-OC43 spike protein. In some embodiments, the coronavirus spike protein comprises an HCoV-HKU1 spike protein.

[0100] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:2. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO:2. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO:2. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO:2. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO:2. In some embodiments, the polypeptide comprises SEQ ID NO:2.

[0101] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:4. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO:4. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO:4. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO:4. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO:4. In some embodiments, the polypeptide comprises SEQ ID NO:4.

[0102] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:6. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO:6. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO:6. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO:6. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO:6. In some embodiments, the polypeptide comprises SEQ ID NO:6.

[0103] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 8. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO: 8. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO: 8. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO: 8. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO: 8. In some embodiments, the polypeptide comprises SEQ ID NO: 8.

[0104] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 10. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO: 10. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO: 10. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO: 10. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO: 10. In some embodiments, the polypeptide comprises SEQ ID NO: 10.

[0105] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 12. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO: 12. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO: 12. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO: 12. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO: 12. In some embodiments, the polypeptide comprises SEQ ID NO: 12.

[0106] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 14. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO: 14. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO: 14. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO: 14. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO: 14. In some embodiments, the polypeptide comprises SEQ ID NO: 14.

[0107] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 16. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO: 16. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO: 16. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO: 16. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO: 16. In some embodiments, the polypeptide comprises SEQ ID NO: 16.

[0108] In some embodiments, the composition further comprises a second treatment for coronavirus infection. In some embodiments, the second treatment comprises an antibiotic, an antiviral, convalescent serum, an immunomodulator, an anticoagulant, a body fluid, oxygen, a corticosteroid, an antibody, GSnP-6, a sialyl Lewis X analog, an antiproliferative agent, a calcineurin inhibitor, an anti-signaling compound, or a combination thereof. In some embodiments, the second treatment comprises an anti-SARS-CoV-2 drug. In some embodiments, the anti-SARS-CoV-2 drug is azithromycin, AC-55541, apicidin, AZ3451, AZ8838, bafilomycin A1, CCT 365623, daunorubicin, E-52862, entacapone, GB110, H-89, haloperidol, indomethacin, JQ1, loratadine, merimepodib, metformin, midostaurin, migalastat, mycophenolic acid, PB28, PD-144418, ponatinib, ribavirin, RS-PPCC, ruxolitinib, RVX-208, S-verapamil, silmitasertib, TMCB, UCPH-101, valproic acid, XL413, ZINC1775962367, ZINC4326719, ZINC4511851, ZINC95559591, 4E2RCat, ABBV-744, camostat, captopril, CB5083, clopidogrel selected from the group consisting of ramphenicol, chloroquine (and / or hydroxychloroquine), CPI-0610, dabrafenib, DBeQ, dBET6, IHVR-19029, linezolid, lisinopril, minoxidil, ML240, MZ1, nafamostat, pevonedistat, PS3061, rapamycin (sirolimus), sanglifehrin A, sapanisertib (INK128 / MlN128), FK-506 (tacrolimus), Ternatin4 (DA3), tigecycline, tomivosertib (eFT-508), veldinexor, WDB002, zotatifine (eFT226), and combinations thereof.

[0109] Disclosed herein, in some embodiments, are pharmaceutical compositions comprising a vector encoding a polypeptide comprising an amino acid sequence having at least 10% identity to SEQ ID NO: 18; and pharmaceutical compositions comprising a vector encoding a polypeptide having an amino acid sequence corresponding to the oligomerization domain of the HIV spike protein and having at least 10% identity to SEQ ID NO: 18.

[0110] In some embodiments, the HIV spike protein comprises the gp160 spike protein of HIV.

[0111] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 18. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO: 18. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO: 18. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO: 18. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO: 18. In some embodiments, the polypeptide comprises SEQ ID NO: 18.

[0112] In some embodiments, the composition further comprises a second treatment for HIV infection. In some embodiments, the second treatment comprises an antibiotic, an antiviral, convalescent serum, an immunomodulator, an anticoagulant, a body fluid, oxygen, a corticosteroid, an antibody, GSnP-6, a sialyl Lewis X analog, an antiproliferative agent, a calcineurin inhibitor, an anti-signaling compound, or a combination thereof. In some embodiments, the second treatment comprises an anti-HIV drug. In some embodiments, the anti-HIV drug is efavirenz (Sustiva), rilpivirine (Edurant), etravirine (Intelence), delavirdine (Rescriptor), nevirapine (Viramune, Viramune) XR), doravirine (Pifeltroz), abacavir (Ziagen), tenofovir alafenamide fumarate (Vemlidy), tenofovir (Viread), emtricitabine (Emtriva), lamivudine (Epivir), zidovudine (Retrovir), abacavir / lamivudine / zidovudine (Trizivir), abacavir / lamivudine (Epzicom), emtricitabine / tenofovir (Truvada), abacavir / lamivudine (Epzicom), lamivudine / tenofovir disoproxil fumarate (Cimduo, Temixys), lamivudine / zidovudine (Combivir), emtricitabine / tenofovir alafenamide (Descovy), didanosine (Videx, Videx) EC), stavudine (Zerit), atazanavir (Reyataz), darunavir (Prezista), fosamprenavir (Lexiva), ritonavir (Norvir), tipranavir (Aptivus), lopinavir / ritonavir (Kaletra), atazanavir / cobicistat (Evotaz), darunavir / cobicistat (Prezcobix), indinavir (Crixivan), nelfinavir (Viracept), saquinavir (Invirase), bictegravir sodium / emtricitabine / tenofovir alafenamidefumar) (Biktarvy), raltegravir (Isentress), elvitegravir (Genvoya and Stribild), dolutegravir (Tivicay), cobicistat (Tybost), ritonavir (Norvir), enfuvirtide (Fuzeon), maraviroc (Selzentry), ibalizumab-uiyk (Trogarzo), maraviroc (Selzentry), fostemsavir (Rukobia), doravirine / lamivudine / tenofovir disoproxil fumarate (Delstrigo), efavirenz / lamivudine / tenofovir disoproxil fumarate (Symfi), efavirenz / lamivudine / tenofovir disoproxil fumarate (Symfi) Lo), efavirenz / emtricitabine / tenofovir disoproxil fumarate (Atripla), emtricitabine / rilpivirine / tenofovir alafenamide fumarate (Odefsey), emtricitabine / rilpivirine / tenofovir disoproxil fumarate (Complera), elvitegravir / cobicistat / emtricitabine / tenofovir disoproxil fumarate (Stribild), elvitegravir / cobicistat / emtricitabine / tenofovir alafenamide fumarate (Genvoya), abacavir / dolutegravir / rilpivir ... Selected from the group consisting of mivudine (Triumeq), bictegravir / emtricitabine / tenofovir alafenamide fumarate (Biktarvy), dolutegravir / lamivudine (Dovato), dolutegravir / rilpivirine (Juluca), darunavir / cobicistat / emtricitabine / tenofovir alafenamide fumarate (Symtuza), acetyl-L-carnitine, whey protein, L-glutamine, L-arginine, hydroxymethylbutyrate (HMB), probiotics, vitamins and minerals, and combinations thereof.

[0113] Disclosed herein, in some embodiments, are pharmaceutical compositions comprising a vector encoding a polypeptide comprising an amino acid sequence having at least 10% identity to SEQ ID NO:20; and pharmaceutical compositions comprising a vector encoding a polypeptide having an amino acid sequence corresponding to the oligomerization domain of the Ebola glycoprotein and having at least 10% identity to SEQ ID NO:20.

[0114] In some embodiments, the Ebola virus glycoprotein comprises the Ebola GP spike protein.

[0115] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 20. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO: 20. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO: 20. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO: 20. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO: 20. In some embodiments, the polypeptide comprises SEQ ID NO: 20.

[0116] In some embodiments, the composition further comprises a second treatment for Ebola infection. In some embodiments, the second treatment comprises an antibiotic, an antiviral, convalescent serum, an immunomodulator, an anticoagulant, a body fluid, oxygen, a corticosteroid, an antibody, GSnP-6, a sialyl Lewis X analog, an antiproliferative agent, a calcineurin inhibitor, an anti-signaling compound, or a combination thereof. In some embodiments, the second treatment comprises an anti-Ebola drug. In some embodiments, the anti-Ebola drug is selected from the group consisting of atoltivimab / maftivimab / odesivimab-ebgn (Inmazeb), ansuvimab-zykl (Ebanga), favipiravir (Avigan), ribavirin, BCX4430, brincidofovir, TKM-Ebola, AVI-7537, JK-05, and combinations thereof.

[0117] Disclosed herein, in some embodiments, are pharmaceutical compositions comprising a vector encoding a polypeptide comprising an amino acid sequence having at least 10% identity to SEQ ID NO:25; and pharmaceutical compositions comprising a vector encoding a polypeptide having an amino acid sequence corresponding to the oligomerization domain of an influenza virus spike protein and having at least 10% identity to SEQ ID NO:25.

[0118] In some embodiments, the influenza comprises an influenza A virus and the influenza virus spike protein comprises an influenza A virus spike protein.

[0119] In some embodiments, the influenza A virus comprises an influenza A / H1 virus, and the influenza virus spike protein comprises an influenza A / H1 virus HA spike protein. In some embodiments, the influenza A virus comprises an influenza A / H3 virus, and the influenza virus spike protein comprises an influenza A / H3 virus HA spike protein. In some embodiments, the influenza comprises an influenza B virus, and the influenza virus spike protein comprises an influenza B virus spike protein. In some embodiments, the influenza B virus comprises an influenza B / Victoria virus, and the influenza virus spike protein comprises an influenza B / Victoria virus HA spike protein. In some embodiments, the influenza B virus comprises an influenza B / Yamagata virus, and the influenza virus spike protein comprises an influenza B / Yamagata virus HA spike protein.

[0120] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 25. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO: 25. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO: 25. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO: 25. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO: 25. In some embodiments, the polypeptide comprises SEQ ID NO: 25.

[0121] In some embodiments, the composition further comprises a second treatment for influenza infection. In some embodiments, the second treatment comprises an antibiotic, an antiviral, convalescent serum, an immunomodulator, an anticoagulant, a body fluid, oxygen, a corticosteroid, an antibody, GSnP-6, a sialyl Lewis X analog, an antiproliferative agent, a calcineurin inhibitor, an anti-signaling compound, or a combination thereof. In some embodiments, the second treatment comprises an anti-influenza drug. In some embodiments, the anti-influenza drug is selected from the group consisting of oseltamivir phosphate (Tamiflu), zanamivir (Relenza), peramivir (Rapivab), baloxavir marboxil (Xofluza), amantadine, rimantadine (Flumadine), umifenovir (Arbidol), moroxydine, fluticare, acetaminophen, chlorpheniramine, dextromethorphan, pseudoephedrine, and combinations thereof.

[0122] Disclosed herein, in some embodiments, are pharmaceutical compositions comprising a vector encoding a polypeptide comprising an amino acid sequence having at least 10% identity to SEQ ID NO: 34; and pharmaceutical compositions comprising a vector encoding a polypeptide having an amino acid sequence corresponding to the oligomerization domain of the RSV glycoprotein and having at least 10% identity to SEQ ID NO: 34.

[0123] In some embodiments, the RSV glycoprotein comprises the F glycoprotein of RSV.

[0124] In some embodiments, the polypeptide has at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 34. In some embodiments, the polypeptide has at least 80% identity to SEQ ID NO: 34. In some embodiments, the polypeptide has at least 85% identity to SEQ ID NO: 34. In some embodiments, the polypeptide has at least 90% identity to SEQ ID NO: 34. In some embodiments, the polypeptide has at least 95% identity to SEQ ID NO: 34. In some embodiments, the polypeptide comprises SEQ ID NO: 34.

[0125] In some embodiments, the composition further comprises a second treatment for the RSV infection. In some embodiments, the second treatment comprises an anti-RSV drug.

[0126] In some embodiments of the compositions disclosed herein, the vector is a viral vector or a non-viral vector. In some embodiments, the vector is a minicircle DNA vector. In some embodiments, the vector genome is 1 x 10 per kg of subject body weight. 8 ~1×10 18 In some embodiments, a dose of about 1 x 10 vector genomes per kg of subject body weight is administered to the subject. 11 ~Approx. 1×10 14 In some embodiments, the dose administered to the subject is about 1 x 10 vector genomes per kg of the subject's body weight. 12 ~Approx. 1×10 15 is administered to the subject.

[0127] In some embodiments of the compositions disclosed herein, the composition further comprises a pharmaceutically acceptable carrier, hi some embodiments, the pharmaceutically acceptable carrier comprises a liposome, a polymeric micelle, a microsphere, or a nanoparticle.

[0128] In some embodiments of the compositions disclosed herein, a single dose of the composition is administered. In some embodiments, multiple doses of the composition are administered. In some embodiments, the composition is delivered to a subject once daily, more than twice daily, more than twice weekly, more than twice monthly, or more than twice yearly. In some embodiments, the composition is delivered systemically or locally. In some embodiments, the composition is administered to a subject by intranasal administration, intravenous administration, intraperitoneal administration, intratracheal administration, intramuscular administration, endoscopic administration, transdermal administration, subcutaneous administration, topical administration, intracranial administration, inhalation, injection, infusion, or perfusion. In some embodiments, the composition is administered to a subject by inhalation. In some embodiments, the composition is administered to a subject by intranasal administration.

[0129] "Individual," "subject," and "patient" are used interchangeably and can refer to a human or non-human.

[0130] As used herein, the terms "treat," "treating," or "treatment" or equivalent terms refer to both therapeutic treatment and prophylactic or preventative measures, where the objective is to prevent or slow (alleviate) undesirable physiological changes or disorders, such as the growth, onset, or spread of diseases, including, but not limited to, viruses. For purposes of this disclosure, beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, reduction in the extent of disease, stabilization of the disease state (i.e., not worsening), delay or slowing of disease progression, improvement or mitigation of the disease state, and remission (whether partial or total), whether detectable or undetectable. "Treatment" also means prolonging survival compared to expected survival if not treated. Patients in need of treatment include those already with a condition or disorder, as well as those prone to having a condition or disorder, or those in whom a condition or disorder is to be prevented. The outcome of treatment can be measured by methods known in the art, such as determining a reduction in viral load or restoration of function.

[0131] Throughout this application, the term "about" is used to indicate that a value includes the inherent variation of error of the measuring or quantitating method.

[0132] The use of "a" or "an" when used with the term "comprising" may mean "one," but is also consistent with the meaning of "one or more," "at least one," and "one or more."

[0133] The phrase "and / or" means "and," "or," or. By way of example, A, B, and / or C includes: A alone, B alone, C alone, A and B in combination, A and C in combination, B and C in combination, A and B in combination with C. In other words, "and / or" acts as an inclusive or.

[0134] The words "comprising" (and any form of comprising, such as "comprises", "comprises"), "having" (and any form of having, such as "have", "has"), "including" (and any form of including, such as "includes", "include") or "containing" (and any form of containing, such as "contains", "contain") are inclusive or open-ended and do not exclude additional, non-repeated elements or method steps.

[0135] Compositions and methods of use thereof can "comprise," "consist essentially of," or "consist of" any of the components or steps disclosed throughout this specification. Compositions and methods "consisting essentially of" any of the disclosed components or steps limit the scope of the claim to the specified materials or steps that do not materially affect the basic and novel characteristics of the claimed disclosure. As used in this specification and claim(s), the words "consisting" (and any form of "consisting" such as "consisting" and "consisting"), "having" (and any form of "having" such as "having" and "having"), "including" (and any form of "comprising" such as "comprising" and "comprising"), or "comprises" (and any form of "comprising" such as "comprising" and "comprising") are inclusive or open-ended and do not exclude additional, non-repeated elements or method steps. It is contemplated that embodiments described herein in the context of the term "comprising" may also be practiced in the context of the term "consisting" or "consisting essentially of."

[0136] Any method in the context of a therapeutic, diagnostic, or physiological purpose or effect may also be described in "use" claim language, such as the "use" of any compound, composition, or agent discussed herein to achieve or carry out the stated therapeutic, diagnostic, or physiological purpose or effect.

[0137] It is specifically contemplated that any limitations discussed with respect to one embodiment of the present disclosure may be applied to any other embodiment of the present disclosure.Furthermore, any composition of the present disclosure may be used in any method of the present disclosure, and any method of the present disclosure may be used to prepare or utilize any composition of the present disclosure.Aspects of the embodiments described in the examples are also embodiments that can be implemented in the context of different examples or embodiments discussed elsewhere in this application, for example, in the abstract, detailed description, claims, and description of the figures.

[0138] Other objects, features, and advantages of the present disclosure will become apparent from the following detailed description. It should be understood, however, that the detailed description and specific examples, while indicating specific embodiments of the present disclosure, are given by way of illustration only, since various changes and modifications within the spirit and scope of the disclosure will become apparent to those skilled in the art from this detailed description. [Brief explanation of the drawings]

[0139] The following drawings form part of the present specification and are included to further demonstrate certain aspects of the present disclosure, which may be better understood by reference to one or more of these drawings in combination with the detailed description of specific embodiments presented herein.

[0140] [Figure 1A-C]Concept of polypeptide-based protein inhibition. Figure 1A shows the domain organization of COVID-19 SARS2-S, mutations in SARS2-S variants, and the design of the inhibitory polypeptides CoV-F1 (F1) and CoV-F2 (F2). SP: signal peptide; NTD: N-terminal domain; RBD: receptor-binding domain; SD1: subdomain 1; SD2: subdomain 2; FP: fusion peptide; HR1: heptad repeat 1; HR2: heptad repeat 2; TM: transmembrane domain; CT: cytoplasmic tail. Cleavage at S1 / S2 (red arrows) generates the N-terminal S1 fragment and the C-terminal S2 fragment. The signal peptide sequences at the N-terminal ends of F1 and F2 enable the polypeptides to be translocated in the same way as COVID-19 SARS2-S. At the C-terminal end, SARS2-S contains the C9 epitope recognized by the C9-rhodopsin antibody 1D4, while both the F1 and F2 polypeptides contain FLAG tags. F1 encompasses SP, HR1, HR2, TM, and CT (residues 911-1273; SEQ ID NO:2), while F2 contains SP, HR2, TM, and CT (residues 985-1273; SEQ ID NO:27). Figure 1B shows a proposed mode of action for polypeptide-based inhibitors targeting coronavirus spike proteins. Top panel: Under normal circumstances, spike proteins are synthesized, folded as monomers, and assembled into native spike oligomers, which are anchored to the surface of virions. Bottom panel: Inhibitory polypeptides disrupt this assembly process, resulting in non-native oligomers with wild-type spike proteins. The net result is a reduced number of native spike oligomers on the surface of new virions.

[0141] [Figure 2A-C]The F1 polypeptide expressed from plasmid DNA significantly reduced the expression and surface translocation of three coronavirus spike glycoproteins. Figure 2A shows the results for COVID-19 SARS-S. The amount of SARS-S protein in whole cell lysates (left) or cell surface fractions (right) was compared for HEK293T cells transfected with a SARS-S-encoding plasmid alone (column #1), together with a 2-fold (column #2) or 10-fold (column #3) molar ratio of a F1-encoding plasmid, or with a 2-fold (column #4) or 10-fold (column #5) molar ratio of a F2-encoding plasmid. Figure 2B shows the results for 2002 SARS-S. The amounts of SARS-S protein in whole cell lysates (left) or cell surface fractions (right) were compared for HEK293T cells transfected with either a SARS-S-encoding plasmid alone (column #1) or a 2-fold (column #2) or 10-fold (column #3) molar ratio of a F1-encoding plasmid. Figure 2C shows the 2012 MERS-S strain. The amounts of MERS-S protein in whole cell lysates (left) or cell surface fractions (right) were compared for HEK293T cells transfected with either a SARS-S-encoding plasmid alone (column #1) or a 2-fold (column #2) or 10-fold (column #3) molar ratio of a F1-encoding plasmid. For all panels, the uncleaved S protein and the cleaved S2 protein were detected by the C9-rhodopsin antibody 1D4. The endogenous membrane protein CNPase was detected by anti-CNPase antibody and served as an internal control. Representative results from at least two independent experiments are shown.

[0142] [Figure 3A-B]Sequence alignment of coronavirus spike proteins. Figure 3A shows an alignment of the SARS2-S spike protein (SARS2), SARS-S spike protein (SARS), and SARS-CoV-2 B.1.1.7-S spike protein (SARS2α). The range of residues contained in the F1 polypeptide is highlighted by a blue box. Figure 3B shows an alignment of the SARS2-S protein (SARS2) and the MERS-S protein (MERS). The range of residues contained in the F1 polypeptide is highlighted by a blue box. The cleavage site between S1 and S2 is indicated by a red arrow. Within S1, the boundary between the NTD and RBD domains is indicated by a green vertical bar. Multiple sequence alignment was performed using CLUSTAL Omega29. The sequences are SARS2-S (GenBank accession number AFR58740.1), SARS-S (GenBank accession number QHD43416.1), B.1.1.7-S (SARS2α-S) (GenBank accession number QQH18545.1), and MERS-S (GenBank accession number QBM11748.1).

[0143] [Figure 4A-D]Sequence conservation of representative viral glycoproteins. Figure 4A shows a comparison of SARS-S and MERS-S proteins with full-length SARS2-S. Figure 4B shows a comparison of a representative human coronavirus spike protein with the SARS2-S F1 polypeptide (residues 911-1273). Figure 4C shows a comparison of the HA proteins of A / H1N1, B / Vic, and B / YM with the full-length A / H3N2 HA. Figure 4D shows a comparison of the A / H1N1 HA, B / Vic HA, and B / YM HA with the A / H3N2 HA polypeptide. In all panels, the number of identical residues (identity), the total residues compared (after " / "), and the corresponding percentage (in parentheses) are shown. The total residues vary slightly due to various gaps in the sequence alignment. The sequences are SARS2-S (GenBank accession number AFR58740.1), SARS-S (GenBank accession number QHD43416.1), SARS2α-S (GenBank accession number QQH18545.1), MERS-S (GenBank accession number QBM11748.1), HCoV-HKU1-S (Uniprot accession number Q0ZME7), HCoV-OC43-S (Uniprot accession number P36334), HCoV-NL63-S (Uniprot accession number Q6Q1S2), and HCoV-229E-S (Uniprot accession number P15423). In panels c) and d), HA sequences were from four influenza vaccine strains from 2019–2020: A / Hawaii / 70 / 2019 (A / H1N1), A / Hong Kong / 45 / 2019 (A / H3N2), B / Washington / 02 / 2019 (B / Vic), and B / Phuket / 3073 / 2013 (B / YM).

[0144] [Figure 5A] Protein expression levels of F1 and F2 polypeptides when plasmids encoding F1 or F2 were co-transfected with a plasmid encoding the coronavirus spike protein for COVID-19 SARS2-S. [Figure 5B]Protein expression levels of F1 and F2 polypeptides when a plasmid encoding F1 or F2 was co-transfected with a plasmid encoding the coronavirus spike protein for 2002 SARS-S. [Figure 5C] Protein expression levels of F1 and F2 polypeptides when plasmids encoding F1 or F2 were cotransfected with a plasmid encoding the coronavirus spike protein of 2012 MERS-S. The endogenous membrane-anchored protein CNPase, detected by anti-CNPase antibody, was used as an internal control. Representative results from two or more independent experiments.

[0145] [Figures 6A-E] The F1 polypeptide expressed from minicircle DNA interacted with the coronavirus spike protein at the protein level. Figure 6A shows the mRNA levels of the spike protein, COVID-19 SARS2-S, measured in the absence or presence of a plasmid encoding F1. Figure 6B shows the mRNA levels of the spike protein, 2002 SARS-S, measured in the absence or presence of a plasmid encoding F1. Figure 6C shows the mRNA levels of the spike protein, 2012 MERS-S, measured in the absence or presence of a plasmid encoding F1. Figure 6D shows a schematic diagram of the FRET setup, in which CFP and YFP were added as tags to the C-terminal ends of SARS2-S and F1, respectively, to yield SARS2-C and F1Y, respectively. Figure 6E shows the FRET ratio of SARS2-C with F1Y (at a 1:1 molar ratio for transfection) compared to the FRET ratio of F1Y alone. ****, p<0.0001 in an unpaired t-test comparing the FRET ratio of SARS2C+F1Y to F1Y alone on a given day for each set of experiments. Numbers in parentheses indicate the number of cells included in each analysis. Results from three independent experiments are shown.

[0146] [Figure 7A] mRNA levels of F1 and F2 when co-transfected with a plasmid encoding the coronavirus spike protein for COVID-19 SARS2-S. [Figure 7B] mRNA levels of F1 and F2 when co-transfected with a plasmid encoding the coronavirus spike protein for 2002 SARS-S. [Figure 7C] mRNA levels of F1 and F2 when cotransfected with a plasmid encoding the coronavirus spike protein for 2012 MERS-S. The mRNA levels of the corresponding proteins in the absence of the plasmid encoding the inhibitory polypeptide were treated as the baseline to which the mRNA levels of other samples were normalized. Error bars represent the standard deviation (SD) from two or more independent experiments.

[0147] [Figure 8A-D] The F1 polypeptide expressed from minicircle DNA significantly reduced the expression and surface translocation of three coronavirus spike glycoproteins. Figure 8A shows a schematic diagram for the construction of the F1 minicircle used in this study. Figure 8B shows results for COVID-19 SARS2-S. Figure 8C shows results for 2002 SARS-S. Figure 8D shows results for 2012 MERS-S. The amounts of uncleaved S and cleaved S2 proteins in whole cell lysates (left) or cell surface fractions (right) are compared for HEK293T cells transfected with either the S-encoding plasmid alone or together with a 4.5-fold or 22.5-fold molar ratio of F1 minicircle. The endogenous membrane-anchored protein CNPase, detected by anti-CNPase antibody, was used as an internal control. Representative results from two or more independent experiments.

[0148] [Figure 9A-B]The F1 polypeptide expressed from minicircle DNA significantly reduced the amount of SARS2-S on the surface of intact pseudovirus and impaired its infectivity. Figure 9A compares the amount of truncated S2 protein for intact pseudovirus produced from HEK293T cells transfected with a SARS2-S-encoding plasmid and various ratios of the empty minicircle control MN501A (columns 1-4) or co-transfected with various ratios of F1 minicircles (columns 5-8). p24, detected by anti-p24 antibody, was used as an internal control. Representative results from two independent experiments are shown in Figure 9B. Pseudoviruses generated in the presence of a 2x molar ratio of F1 minicircles lost their ability to infect hACE2-expressing HEK293T cells. The infectivity of pseudoviruses generated when MN501A minicircles were present at a 2x molar ratio was considered 100% for each cotransfection ratio. Representative results from at least two independent experiments are shown. Error bars represent standard deviation (SD) from two independent experiments.

[0149] [Figure 10A-C]Schematic diagram of generalized polypeptide-based protein inhibition. Figure 10A shows a homo-oligomer. Under normal circumstances, a protein is first synthesized and folded as a monomer, and then multiple monomers (shown in blue and green, but different monomers of the same protein species are shown in the same shape) are assembled into a native protein complex. In the context of polypeptide-based protein interference, an interfering polypeptide (shown in blue) derived from or containing one or more segments of a target protein (shown in blue) in a native protein complex or its homologs competes with the target protein to interact with its native interaction partner (which is identical to the target protein in sequence and structure, shown in green), preventing the formation of the native protein complex, thereby resulting in a non-native protein complex and thus regulating the level of assembled native protein complex. 10B shows that for hetero-oligomers, under normal circumstances, proteins are first synthesized and folded, and then multiple protein species (shown in blue and orange, with different shapes for different protein species) assemble into native protein complexes. In the context of polypeptide-based protein interference, an interfering polypeptide (shown in blue) derived from or containing one or more segments of a target protein (shown in blue) in a native protein complex or its homologs competes with the target protein to interact with its native interaction partner (shown in orange), preventing the formation of the native protein complex, thereby resulting in a non-native protein complex and thus regulating the level of assembled native protein complexes.Figure 10C shows several types of hetero-oligomeric native protein complexes containing multiple copies of a target protein (shown in blue and green) and other protein species (shown in orange). Under normal circumstances, the proteins are first synthesized, folded, and then assembled into native protein complexes. In the context of polypeptide-based protein interference, an interfering polypeptide (shown in blue) derived from or containing one or more segments of the target protein (shown in blue) in the native protein complex or its homologs competes with the target protein to interact with its native interaction partner (shown in green and orange), preventing the formation of the native protein complex, thereby resulting in a non-native protein complex and thus regulating the level of assembled native protein complexes. Polypeptide-based protein interference can cause down- or up-regulation of target pathways.

[0150] [Figure 11] The inhibitory polypeptide gp160i significantly reduced the expression of the HIV-1 gp160 glycoprotein. The amounts of uncleaved gp160 and cleaved gp41 proteins in whole cell lysates were compared for HEK293T cells transfected with a gp160-encoding plasmid alone or together with five times the amount of a gp160i-encoding plasmid. Uncleaved gp160 and cleaved gp41 were detected with the C9-rhodopsin antibody 1D4, and the endogenous membrane protein CNPase was detected with an anti-CNPase antibody, which served as an internal control. Representative results from two or more independent experiments.

[0151] [Figure 12]The inhibitory polypeptide GPi significantly reduced the expression and translocation of Ebola GP glycoprotein. The amounts of uncleaved GP and cleaved GP2 proteins in whole cell lysates (left) or on the cell surface (right) were compared for HEK293T cells transfected with a GP-containing plasmid alone or together with a 5-fold or 15-fold molar ratio of a plasmid encoding GPi. Uncleaved GP and cleaved GP2 were detected with the C9-rhodopsin antibody 1D4, and the endogenous membrane protein CNPase was detected with an anti-CNPase antibody, which served as an internal control. Representative results from two or more independent experiments.

[0152] [Figure 13] The inhibitory polypeptide HAi significantly reduced the expression and translocation of the influenza A and B virus glycoprotein hemagglutinin (HA). The amount of uncleaved HA protein in whole cell lysates (left) or on the cell surface (right) was compared for HEK293T cells transfected with a plasmid encoding HA alone or together with five times the amount of a plasmid encoding HAi. Uncleaved HA was detected with the C9-rhodopsin antibody 1D4, and the endogenous membrane protein CNPase was detected with an anti-CNPase antibody, serving as an internal control. Results for A / H1 HA are shown as an example. Representative results from two or more independent experiments.

[0153] [Figure 14] The inhibitory polypeptide Fi significantly reduced the expression and translocation of RSV type A glycoprotein F. The amount of uncleaved RSV F protein in whole cell lysates (left) or on the cell surface (right) was compared for HEK293T cells transfected with a plasmid encoding RSV F alone or together with a 5-fold or 15-fold molar ratio of a plasmid encoding Fi. Uncleaved RSV F was detected with the C9-rhodopsin antibody 1D4, and the endogenous membrane protein CNPase was detected with an anti-CNPase antibody and served as an internal control. Representative results from two or more independent experiments.

[0154] [Figure 15A-D] The F1 polypeptide expressed from minicircle DNA effectively blocked the replication of authentic SARS-CoV-2 virus in hACE2 mice. Figure 15A shows the experimental setup for the in vivo protection study of the F1 polypeptide in hACE2 mice. Figure 15B shows the weight change of the two mouse groups. Figure 15C shows a boxplot showing the SARS-CoV-2 viral load in the lungs of mice in the two experimental groups. Each dot represents one mouse, and the "x" indicates the mean. p values ​​are reported for unpaired two-tailed t-tests comparing the viral loads of these two groups (n=6). Figure 15D shows H&E staining of mouse lung tissue sections 3 days post-inoculation comparing the two experimental groups.

[0155] [Figure 16A] As used herein, the amino acid sequence of CoV-F1 (F1). [Figure 16B] As used herein, the amino acid sequence of CoV-F2 (F2). [Figure 16C] As used herein, the amino acid sequence of HIV gp160i. [Figure 16D] As used herein, the amino acid sequence of Ebola GPi. [Figure 16E] As used herein, the amino acid sequence of RSV Fi. [Figure 16F]As used herein, the amino acid sequence of influenza HAi is shown. Single-letter codes are used for amino acids. The sequences were derived from SARS2-S (GenBank accession number AFR58740.1), HIV-1 gp160 (GenBank accession number NP_057856.1), Zaire EBOV GP (GenBank accession number AAN37507.1), type A RSV F (GenBank accession number QKN22797.1), and A / Hong Kong / 45 / 2019 (H3N2) influenza virus HA. The signal peptide sequence is highlighted in bold at the N-terminus. The FLAG tag at the C-terminal end of each polypeptide contains a FLAG tag and a tag containing two streps preceding the FLAG tag (not shown). The underlined residues in RSV Fi represent the introduced linker. DETAILED DESCRIPTION OF THE INVENTION

[0156] The present disclosure fulfills various specific needs in the fields of medicine and virology by providing compositions and methods for polypeptide-based inhibition and for utilizing polypeptide-based inhibition in the treatment and prevention of various diseases, including, but not limited to, viral infections (e.g., coronavirus, HIV, Ebola, RSV, or influenza infections) and / or post-viral syndromes, and is based, at least in part, on the surprising discovery that polypeptide-based inhibition is a powerful and innovative strategy for reducing cell surface translocation of viral spike proteins and impairing the ability of viral progeny to infect host cells. The novel compositions and methods of the present invention require engineered regulatory polypeptides directed against proteins and are widely applicable as innovative and efficient solutions for post-translational modulation of protein levels in vitro and in vivo without irreversible genetic modifications.

[0157] As described herein, inhibitory polypeptides designed based on the glycoprotein sequences of the COVID-19 SARS-CoV-2 virus and influenza A / H3N2 virus were unexpectedly found to be equally effective against glycoproteins from other coronavirus and influenza strains, respectively, despite a low sequence identity of as little as 27%. This highlights their high insensitivity to mutations and potent activity against glycoproteins from different lineages of viruses. Indeed, surprisingly, in hACE2 mice infected with authentic SARS-CoV-2 virus, a single dose of DNA encoding the inhibitory polypeptide effectively prevented viral replication in the mouse lungs. Moreover, due at least in part to its reduced sequence size, the minicircle encoding the inhibitory polypeptide can withstand the shear forces involved in aerosol generation, enabling convenient and effective nasal spray delivery. 27 Thus, in some embodiments, the compositions and related methods disclosed herein can provide the basis for highly effective broad-spectrum antiviral therapeutics. Moreover, these approaches represent a general method for post-translationally altering protein expression of essentially any protein, thus providing a straightforward and highly precise approach for treating infectious or non-infectious diseases.

[0158] For RNA viruses, including coronaviruses, the high mutation rate of the virus is a powerful weapon for repeated infections among human populations, as exemplified by the recent SARS2-S variant. 3、4、7、8、9Accumulating mutations in the S1 region allow evasion from neutralizing antibodies elicited by natural infection or vaccines (Figure 1A). The S2 region of these spike proteins is generally more constant in evolution. Therefore, polypeptide-based inhibitors that exploit highly conserved sequences in viral proteins can be used to develop novel therapeutic agents with high efficacy and target specificity, broad-spectrum applicability, and adaptability to other viral proteins, including, but not limited to, other viral membrane-fusion glycoproteins, to combat viral pathogens.

[0159] Furthermore, the polypeptide-based protein inhibition described herein provides a general method for post-translational regulation of native protein complexes. In this case, interactions within the complex can be regulated by polypeptides derived from or containing one or more segments of a target protein in a native portein complex or its homologs ( FIG. 10 ), for example, by polypeptides derived from or containing one or more segments of a target protein in the spike protein complexes of HIV, Ebola, RSV, and influenza viruses. Compared with smaller organic compounds, the relatively larger interaction surface of polypeptides allows such polypeptide-based inhibition to provide therapeutic agents with high efficacy and specificity, and polypeptides can be easily designed or selected without structural information. Additionally, polypeptides derived from one or more segments of host proteins are essentially immunogenically inactive.

[0160] Various aspects of the present disclosure are based on compositions comprising protein-interacting polypeptides (referred to herein as "interfering polypeptides" or "protein-interfering polypeptides"), such as the protein-interacting polypeptides characterized by Figures 16A-16E, that interact with, and in some cases interfere with, proteins such as viral proteins, including, but not limited to, viral spike proteins, including coronavirus spike protein, HIV spike protein, Ebola virus glycoprotein, RSV glycoprotein, and influenza virus spike protein, and methods of administering such polypeptides; however, polypeptides that interact with other viral and non-viral proteins are also contemplated and within the scope of the present disclosure. Certain polypeptides of the present disclosure inhibit the formation and translocation of viral spike proteins to the cell surface of a subject and / or to the viral envelope. Certain polypeptides of the present disclosure oligomerize with the conserved oligomerization domain of viral spike proteins to inhibit the formation and translocation of viral spike proteins to the cell surface of a subject and / or to the viral envelope. Certain polypeptides of the present disclosure reduce the amount of viral spike proteins on the cell surface of a subject and / or on the surface of the viral envelope. Certain polypeptides of the present disclosure oligomerize with the conserved oligomerization domain of a viral spike protein to reduce the amount of the viral spike protein on the cell surface of a subject and / or on the surface of the viral envelope. In some cases, inhibiting the formation and transfer of the viral spike protein to the cell surface of a subject and / or to the viral envelope and / or reducing the amount of the viral spike protein on the cell surface of a subject and / or on the surface of the viral envelope treats or prevents viral infection and / or post-viral infection syndrome.Such polypeptides are therefore useful, for example, in methods for the treatment and prevention of viral infections, such as coronavirus infections (e.g., MERS-CoV infection, SARS-CoV infection and SARS-CoV-2 infection) and / or post-coronavirus syndrome, HIV infection, Ebola infection, RSV infection, and / or influenza infection, or other diseases unrelated to viral infection in which polypeptide-based protein inhibition would be beneficial.

[0161] I. Protein-Interacting Polypeptide Compositions Aspects of the present disclosure relate to polypeptides that interact with, and in some cases inhibit or interfere with, a target protein and / or its natural interaction partners ("protein-interacting polypeptides" or "inhibitory polypeptides" or "interfering polypeptides" or "interacting polypeptides" or "protein-interfering polypeptides"), including, but not limited to, viral proteins such as viral spike proteins in vivo, compositions comprising such polypeptides, and methods of using the polypeptides to treat and prevent diseases or conditions in a subject, including, but not limited to, viral (e.g., coronavirus, HIV, Ebola, RSV, influenza) infections.

[0162] As disclosed herein, "interacting with" refers to any contact at the interaction surface of a protein-interacting polypeptide and a target protein and / or a natural interaction partner of the target protein, including, but not limited to, oligomerization of a protein-interacting polypeptide with a corresponding oligomerization domain of the target protein and / or a natural interaction partner of the target protein. For example, in some cases, "interacting with" can refer to any contact between a protein-interacting polypeptide and a target protein, a protein-interacting polypeptide and a natural interaction partner of the target protein, and / or a protein-interacting polypeptide and a target protein and a natural interaction partner of the target protein. In some cases, "interacting with" can refer to oligomerization of a protein-interacting polypeptide and a target protein, a protein-interacting polypeptide and a natural interaction partner of the target protein, and / or a protein-interacting polypeptide and a target protein and a natural interaction partner of the target protein. In certain embodiments, "interacting with" can refer to any contact between a viral protein-interacting polypeptide and a viral protein, including, but not limited to, oligomerization of a viral protein-interacting polypeptide with a corresponding oligomerization domain of the viral protein.

[0163] In some cases, such interaction between a protein-interacting polypeptide and a target protein and / or a natural interaction partner of the target protein at an interaction surface may be inhibiting or interfering. As disclosed herein, "inhibit," "inhibitory," "inhibition," "interference," "interfering," and related terms and phrases refer to contact between a protein-interacting polypeptide, a target protein, and / or a natural interaction partner of the target protein that prevents natural protein complex formation, including, but not limited to, competition of the protein-interacting polypeptide with the target protein for interaction with the natural interaction partner of the target protein. In some cases, "inhibit," "inhibitory," "inhibition," "interference," "interfering," and related terms and phrases may refer to oligomerization of a protein-interacting polypeptide with a corresponding oligomerization domain of the target protein and / or a natural interaction partner of the target protein that prevents natural oligomeric protein complex formation, including, but not limited to, competition of the protein-interacting polypeptide with the target protein for interaction with the corresponding oligomerization domain of the natural interaction partner of the target protein. In certain embodiments, "inhibit," "inhibitory," "inhibition," or "interfere" may refer to contact between a viral protein-interacting polypeptide and a viral protein such that the viral protein-interacting polypeptide competes with the corresponding oligomerization domain of the viral protein.

[0164] As disclosed herein, a "protein-interacting polypeptide" refers to any polypeptide that can interact with, and in some cases inhibit or interfere with, a target protein and / or a target protein's natural interaction partner. For example, a protein-interacting polypeptide can be a viral protein-interacting polypeptide that interacts with, inhibits, or interferes with a viral protein, such as the viral spike glycoprotein and / or other viral proteins.

[0165] As disclosed herein, a "target protein" refers to a protein from which the amino acid sequence of a protein-interacting polypeptide disclosed herein is derived, and which has at least 10% amino acid sequence identity with the protein-interacting polypeptide.

[0166] In some cases, the "target protein" is a monomer of a homo-oligomeric protein complex, and interaction or contact of the protein-interacting polypeptide with the protein monomer inhibits native homo-oligomeric complex formation (see, e.g., Figure 10A). In such cases, the protein-interacting polypeptide competes with the monomer to prevent native homo-oligomeric complex formation by the target monomer and additional monomers, thereby modulating the monomer and / or its biological function.

[0167] In some cases, the "target protein" is a naturally occurring protein, and the interaction or contact of the protein-interacting polypeptide with the naturally occurring protein's natural interaction partner prevents further interaction of the naturally occurring protein with the naturally occurring protein's natural interaction partner (see, e.g., Figure 10B). In such cases, the protein-interacting polypeptide competes with the naturally occurring protein for binding to the naturally occurring protein's natural interaction partner, preventing the naturally occurring protein from forming a natural hetero-oligomeric complex, thereby modulating the naturally occurring protein and / or its biological function.

[0168] In some cases, the "target protein" is a naturally occurring protein, and the interaction or contact of the protein-interacting polypeptide with the naturally occurring protein and / or the naturally occurring protein's natural interaction partners prevents further interactions of the naturally occurring protein with other naturally occurring proteins and / or the naturally occurring protein's natural interaction partners (see, e.g., Figure 10C). In such cases, the protein-interacting polypeptide competes with the naturally occurring protein for binding to the naturally occurring protein and / or the naturally occurring interaction partners, preventing the naturally occurring protein from forming a natural hetero-oligomeric complex, thereby modulating the naturally occurring protein and / or its biological function.

[0169] The amino acid sequences of the protein-interacting polypeptides disclosed herein may be derived from one or more "target proteins" to achieve modulation of a native protein complex. Furthermore, one or more "protein-interacting polypeptides" may be used to modulate a native protein complex, and one or more "protein-interacting polypeptides" may be used to modulate one or more native protein complexes.

[0170] As disclosed herein, "natural interaction partner of a target protein," "natural interaction partner of a native protein," and the like refer to one or more proteins that associate with a native protein in a cell to form a native protein complex.

[0171] Upon binding of the interacting polypeptide at the interaction surface, the protein-interacting polypeptide can block and inhibit or interfere with the homo-oligomerization of the target protein or its interaction with itself, and / or upon binding of the interacting polypeptide at the interaction surface, the protein-interacting polypeptide can block and inhibit or interfere with the hetero-oligomerization of the target protein or its interaction with its natural interaction partner. As a result of such interactions, polypeptides that can be derived from or contain one or more segments of the target protein in a natural protein complex or its homologue compete with the target protein, resulting in a non-natural protein complex and thus modulating the level of the assembled natural protein complex. Such polypeptide-based protein inhibition or interference can result in down- or up-regulation of the target pathway.

[0172] As used herein, "regulating," "regulate," "regulation," and grammatical equivalents refer to the modulation of a target protein and / or its biological function, thereby enabling a cell to regulate not only the amount but also the activity of its protein components. Naturally occurring protein complexes consist of multiple independent polypeptide subunits. In some homo-oligomeric embodiments, the protein subunits of a naturally occurring protein complex are identical. In other hetero-oligomeric embodiments, the protein subunits of a naturally occurring protein complex are two or more different polypeptides. In either case, interactions between the polypeptides are important in regulating protein activity.

[0173] In some embodiments, "modulation" of a target protein and / or its biological function includes inhibition of the target protein and / or its biological function. As used herein, the terms "reduce," "inhibit," "diminish," "suppress," and grammatical equivalents (including "less," "smaller," etc.) refer to a measurable, in some cases statistically significant, decrease in occurrence or activity, including a complete blockage of occurrence or activity. For example, activity can refer to one or more biological activities of a native protein and / or native protein complex, and occurrence can refer to the formation of a native protein complex. For example, "inhibition" can refer to about a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% decrease in activity or occurrence. These terms can be used in reference to a "control" that has not undergone a particular treatment, e.g., a method of the present disclosure. In one example, the control can be an untreated sample or subject. In another example, the control can be a sample or subject that has undergone a treatment that is different from the treated sample or subject. In some embodiments, a "treated" sample or subject is one that has been subjected to a method of the present disclosure.

[0174] In some embodiments, "modulation" and / or "inhibition" of a target protein and / or its biological function comprises impaired biological activity of the target protein and / or native protein complex upon formation of a non-native protein complex. In some embodiments, "modulation" and / or "inhibition" of a target protein and / or its biological function comprises proteasomal degradation of non-native protein complexes that are loosely packed and disrupt cellular quality control systems upon formation of the non-native protein complex.

[0175] Thus, in some embodiments, modulating a target protein or its biological function in vivo, including but not limited to, a viral protein such as, but not limited to, a coronavirus spike protein, an HIV spike protein, an Ebola glycoprotein, an RSV glycoprotein, and / or an influenza virus spike protein, includes inhibiting a target protein or its biological function in vivo, including but not limited to, a viral protein such as, but not limited to, a coronavirus spike protein, an HIV spike protein, an Ebola glycoprotein, an RSV glycoprotein, and / or an influenza virus spike protein. In some embodiments, inhibiting a target protein or its biological function in vivo, including but not limited to, a viral protein such as, but not limited to, a coronavirus spike protein, an HIV spike protein, an Ebola glycoprotein, an RSV glycoprotein, and / or an influenza virus spike protein, includes impairing the biological activity of the target protein upon formation of a non-native protein complex and / or a naturally occurring protein complex comprising the target protein. In some embodiments, inhibition of a target protein or its biological function in vivo, including but not limited to a viral protein such as a coronavirus spike protein, an HIV spike protein, an Ebola glycoprotein, an RSV glycoprotein, and / or an influenza virus spike protein, comprises proteasomal degradation of the target protein upon formation of a non-native protein complex and / or a native protein complex comprising the target protein.

[0176] Certain embodiments relate to polypeptides having an amino acid sequence corresponding to that of a target protein, wherein the amino acid sequence has at least 10% sequence identity with the corresponding sequence of the target protein. Certain embodiments relate to polypeptides having an amino acid sequence corresponding to the oligomerization domain of the target protein, wherein the amino acid sequence has at least 10% sequence identity with the oligomerization domain of the target protein.

[0177] Certain aspects relate to polypeptides having an amino acid sequence having at least 10-80% identity to SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, or 16. Certain aspects relate to polypeptides having an amino acid sequence corresponding to the oligomerization domain of a coronavirus spike protein, wherein the amino acid sequence has at least 10-80% identity to SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, or 16.

[0178] Particular embodiments relate to polypeptides having an amino acid sequence that has at least 10-80% identity to SEQ ID NO: 18. Particular embodiments relate to polypeptides having an amino acid sequence that corresponds to the sequence of an HIV spike protein, wherein the amino acid sequence has at least 10-80% identity to SEQ ID NO: 18.

[0179] Particular embodiments relate to polypeptides having an amino acid sequence that has at least 10-80% identity to SEQ ID NO: 20. Particular embodiments relate to polypeptides having an amino acid sequence that corresponds to the sequence of an Ebola virus glycoprotein, wherein the amino acid sequence has at least 10-80% identity to SEQ ID NO: 20.

[0180] Particular embodiments relate to polypeptides having an amino acid sequence that has at least 10-80% identity to SEQ ID NO: 25. Particular embodiments relate to polypeptides having an amino acid sequence that corresponds to the sequence of an influenza virus HA spike protein, wherein the amino acid sequence has at least 10-80% identity to SEQ ID NO: 25.

[0181] Certain embodiments relate to polypeptides having an amino acid sequence having at least 10-80% identity to SEQ ID NO: 33. Certain embodiments relate to polypeptides having an amino acid sequence corresponding to the sequence of an RSV glycoprotein, wherein the amino acid sequence has at least 10-80% identity to SEQ ID NO: 34.

[0182] In some embodiments, the polypeptide has an amino acid sequence corresponding to the sequence of a target protein, and the amino acid sequence is at least 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126 , 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 1 89, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 22 0, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251 , 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282,283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, ​​383, 384, 41, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, ​​383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399 , 400, or more amino acids, or any value derivable therein, and having at least 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 110%, 111%, 120%, 121%, 122%, 123%, 124%, 125%, 126%, 127%, 128%, 129%, 130%, 131%, 132%, In some embodiments, the polypeptide has an amino acid sequence corresponding to the sequence of a target protein, the amino acid sequence being:The polypeptide has an amino acid sequence corresponding to the sequence of the target protein, wherein the amino acid sequence has at least 30 amino acids and has 10% sequence identity with the sequence of the target protein, or a fragment or functional derivative thereof. In some embodiments, the polypeptide has an amino acid sequence corresponding to the sequence of the target protein, wherein the amino acid sequence has at least 30 amino acids and has 20% sequence identity with the sequence of the target protein, or a fragment or functional derivative thereof. In some embodiments, the polypeptide has an amino acid sequence corresponding to the sequence of the target protein, wherein the amino acid sequence has at least 30 amino acids and has 30% sequence identity with the sequence of the target protein, or a fragment or functional derivative thereof. In some embodiments, the polypeptide has an amino acid sequence corresponding to the sequence of the target protein, wherein the amino acid sequence has at least 30 amino acids and has 40% sequence identity with the sequence of the target protein, or a fragment or functional derivative thereof. In some embodiments, the polypeptide has an amino acid sequence corresponding to the sequence of the target protein, wherein the amino acid sequence has at least 30 amino acids and has 50% sequence identity with the sequence of the target protein, or a fragment or functional derivative thereof. In some embodiments, the polypeptide has an amino acid sequence corresponding to the sequence of a target protein, the amino acid sequence having at least 30 amino acids and having 60% sequence identity with the sequence of the target protein or a fragment or functional derivative thereof. In some embodiments, the polypeptide has an amino acid sequence corresponding to the sequence of a target protein, the amino acid sequence having at least 30 amino acids and having 70% sequence identity with the sequence of the target protein or a fragment or functional derivative thereof. In some embodiments, the polypeptide has an amino acid sequence corresponding to the sequence of a target protein, the amino acid sequence having at least 30 amino acids and having at least 75% sequence identity with the sequence of the target protein or a fragment or functional derivative thereof. In some embodiments, the polypeptide has an amino acid sequence corresponding to the sequence of a target protein, the amino acid sequence having at least 30 amino acids and having at least 80% sequence identity with the sequence of the target protein or a fragment or functional derivative thereof. In some embodiments, the polypeptide has an amino acid sequence corresponding to the sequence of a target protein,The amino acid sequence has at least 30 amino acids and has at least 85% sequence identity with the sequence of the target protein, or a fragment or functional derivative thereof. In some embodiments, a polypeptide has an amino acid sequence corresponding to the sequence of a target protein, the amino acid sequence having at least 30 amino acids and having at least 90% sequence identity with the sequence of the target protein, or a fragment or functional derivative thereof. In some embodiments, a polypeptide has an amino acid sequence corresponding to the sequence of a target protein, the amino acid sequence having at least 30 amino acids and having at least 95% sequence identity with the sequence of the target protein, or a fragment or functional derivative thereof. In some embodiments, a polypeptide having an amino acid sequence corresponding to the sequence of a target protein comprises, consists of, or consists essentially of the sequence of the target protein, or a fragment or functional derivative thereof.

[0183] In some embodiments, the polypeptide has an amino acid sequence corresponding to an oligomerization domain of a target protein, wherein the amino acid sequence is at least 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 1109, 1110, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 13 1, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124 , 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 1 87, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218 8, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249 ,250,251,252,253,254,255,256,257,258,259,260,261,262,263,264,265,266,267,268,269,270,271,272,273,274,275,276,277,278,279,280,281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 40, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, ​​383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399 , 400, or more amino acids, or any value derivable therein, and having at least 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 110%, 111%, 120%, 121%, 122%, 123%, 124%, 125%, 126%, 127%, 128%, 129%, 130%, 131%, 132%, In some embodiments, the polypeptide has 9%, 50%, 51%, 52%, 52%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity, or any value derivable therein.The polypeptide has an amino acid sequence corresponding to the oligomerization domain of the target protein, the amino acid sequence having at least 30 amino acids and having 10% sequence identity with the oligomerization domain of the target protein, or a fragment or functional derivative thereof. In some embodiments, the polypeptide has an amino acid sequence corresponding to the oligomerization domain of the target protein, the amino acid sequence having at least 30 amino acids and having 20% ​​sequence identity with the oligomerization domain of the target protein, or a fragment or functional derivative thereof. In some embodiments, the polypeptide has an amino acid sequence corresponding to the oligomerization domain of the target protein, the amino acid sequence having at least 30 amino acids and having 30% sequence identity with the oligomerization domain of the target protein, or a fragment or functional derivative thereof. In some embodiments, the polypeptide has an amino acid sequence corresponding to the oligomerization domain of the target protein, the amino acid sequence having at least 30 amino acids and having 40% sequence identity with the oligomerization domain of the target protein, or a fragment or functional derivative thereof. In some embodiments, the polypeptide has an amino acid sequence corresponding to an oligomerization domain of a target protein, the amino acid sequence having at least 30 amino acids and having 50% sequence identity with the oligomerization domain of the target protein, or a fragment or functional derivative thereof. In some embodiments, the polypeptide has an amino acid sequence corresponding to an oligomerization domain of a target protein, the amino acid sequence having at least 30 amino acids and having 60% sequence identity with the oligomerization domain of the target protein, or a fragment or functional derivative thereof. In some embodiments, the polypeptide has an amino acid sequence corresponding to an oligomerization domain of a target protein, the amino acid sequence having at least 30 amino acids and having 70% sequence identity with the oligomerization domain of the target protein, or a fragment or functional derivative thereof. In some embodiments, the polypeptide has an amino acid sequence corresponding to an oligomerization domain of a target protein, the amino acid sequence having at least 30 amino acidsThe polypeptide has an amino acid sequence corresponding to the oligomerization domain of the target protein, or a fragment or functional derivative thereof, which has at least 75% sequence identity. In some embodiments, the polypeptide has an amino acid sequence corresponding to the oligomerization domain of the target protein, which has at least 30 amino acids and has at least 80% sequence identity to the oligomerization domain of the target protein, or a fragment or functional derivative thereof. In some embodiments, the polypeptide has an amino acid sequence corresponding to the oligomerization domain of the target protein, which has at least 30 amino acids and has at least 85% sequence identity to the oligomerization domain of the target protein, or a fragment or functional derivative thereof. In some embodiments, the polypeptide has an amino acid sequence corresponding to the oligomerization domain of the target protein, which has at least 30 amino acids and has at least 90% sequence identity to the oligomerization domain of the target protein, or a fragment or functional derivative thereof. In some embodiments, the polypeptide has an amino acid sequence corresponding to an oligomerization domain of a target protein, wherein the amino acid sequence has at least 30 amino acids and has at least 95% sequence identity with the oligomerization domain of the target protein, or a fragment or functional derivative thereof. In some embodiments, the polypeptide having an amino acid sequence corresponding to the oligomerization domain of the target protein comprises, consists of, or consists essentially of the oligomerization domain of the target protein, or a fragment or functional derivative thereof.

[0184] In some embodiments, a protein, e.g., a polypeptide that interacts with a coronavirus spike protein, has at least 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, or 48% identity with SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, or 16, or a fragment or functional derivative thereof. , 48%, 49%, 50%, 51%, 52%, 52%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity, or any value derivable therein.

[0185] In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 10% sequence identity to SEQ ID NO:2, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 20% sequence identity to SEQ ID NO:2, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 30% sequence identity to SEQ ID NO:2, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 40% sequence identity to SEQ ID NO:2, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 50% sequence identity to SEQ ID NO:2, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 60% sequence identity to SEQ ID NO:2, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO:2, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 75% sequence identity to SEQ ID NO:2, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO:2, or a fragment or functional derivative thereof.In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:2, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:2, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO:2, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises, consists of, or consists essentially of SEQ ID NO:2, or a fragment or functional derivative thereof.

[0186] In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 10% sequence identity to SEQ ID NO:4, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 20% sequence identity to SEQ ID NO:4, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 30% sequence identity to SEQ ID NO:4, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 40% sequence identity to SEQ ID NO:4, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 50% sequence identity to SEQ ID NO:4, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 60% sequence identity to SEQ ID NO:4, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO: 4, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 75% sequence identity to SEQ ID NO: 4, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 4, or a fragment or functional derivative thereof.In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 4, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 4, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 4, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises, consists of, or consists essentially of SEQ ID NO: 4, or a fragment or functional derivative thereof.

[0187] In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 10% sequence identity to SEQ ID NO:6, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 20% sequence identity to SEQ ID NO:6, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 30% sequence identity to SEQ ID NO:6, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 40% sequence identity to SEQ ID NO:6, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 50% sequence identity to SEQ ID NO:6, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 60% sequence identity to SEQ ID NO:6, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO:6, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 75% sequence identity to SEQ ID NO:6, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO:6, or a fragment or functional derivative thereof.In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:6, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:6, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO:6, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises, consists of, or consists essentially of SEQ ID NO:6, or a fragment or functional derivative thereof.

[0188] In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 10% sequence identity to SEQ ID NO:8, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 20% sequence identity to SEQ ID NO:8, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 30% sequence identity to SEQ ID NO:8, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 40% sequence identity to SEQ ID NO:8, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 50% sequence identity to SEQ ID NO:8, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 60% sequence identity to SEQ ID NO:8, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO: 8, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 75% sequence identity to SEQ ID NO: 8, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 8, or a fragment or functional derivative thereof.In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 8, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 8, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 8, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises, consists of, or consists essentially of SEQ ID NO: 8, or a fragment or functional derivative thereof.

[0189] In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 10% sequence identity to SEQ ID NO: 10, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 20% sequence identity to SEQ ID NO: 10, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 30% sequence identity to SEQ ID NO: 10, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 40% sequence identity to SEQ ID NO: 10, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 50% sequence identity to SEQ ID NO: 10, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 60% sequence identity to SEQ ID NO: 10, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO: 10, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 75% sequence identity to SEQ ID NO: 10, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 10, or a fragment or functional derivative thereof.In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 10, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 10, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 10, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises, consists of, or consists essentially of SEQ ID NO: 10, or a fragment or functional derivative thereof.

[0190] In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 10% sequence identity to SEQ ID NO: 12, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 20% sequence identity to SEQ ID NO: 12, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 30% sequence identity to SEQ ID NO: 12, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 40% sequence identity to SEQ ID NO: 12, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 50% sequence identity to SEQ ID NO: 12, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 60% sequence identity to SEQ ID NO: 12, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO: 12, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 75% sequence identity to SEQ ID NO: 12, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 12, or a fragment or functional derivative thereof.In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 12, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 12, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 12, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises, consists of, or consists essentially of SEQ ID NO: 12, or a fragment or functional derivative thereof.

[0191] In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 10% sequence identity to SEQ ID NO: 14, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 20% sequence identity to SEQ ID NO: 14, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 30% sequence identity to SEQ ID NO: 14, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 40% sequence identity to SEQ ID NO: 14, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 50% sequence identity to SEQ ID NO: 14, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 60% sequence identity to SEQ ID NO: 14, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO: 14, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 75% sequence identity to SEQ ID NO: 14, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 14, or a fragment or functional derivative thereof.In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 14, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 14, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 14, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises, consists of, or consists essentially of SEQ ID NO: 14, or a fragment or functional derivative thereof.

[0192] In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 10% sequence identity to SEQ ID NO: 16, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 20% sequence identity to SEQ ID NO: 16, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 30% sequence identity to SEQ ID NO: 16, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 40% sequence identity to SEQ ID NO: 16, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 50% sequence identity to SEQ ID NO: 16, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 60% sequence identity to SEQ ID NO: 16, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO: 16, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 75% sequence identity to SEQ ID NO: 16, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 16, or a fragment or functional derivative thereof.In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 16, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 16, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 16, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with coronavirus spike protein, comprises, consists of, or consists essentially of SEQ ID NO: 16, or a fragment or functional derivative thereof.

[0193] In some embodiments, a polypeptide that interacts with a protein, e.g., an HIV spike protein, has at least 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 110%, 111%, 112%, 113%, 114%, 115%, 116%, 117%, 118%, 119%, 120%, 121%, 122%, 123%, 124 , 51%, 52%, 52%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity, or any value derivable therein.

[0194] In some embodiments, a protein, e.g., a polypeptide that interacts with HIV spike protein, comprises an amino acid sequence having at least 10% sequence identity to SEQ ID NO: 18, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with HIV spike protein, comprises an amino acid sequence having at least 20% sequence identity to SEQ ID NO: 18, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with HIV spike protein, comprises an amino acid sequence having at least 30% sequence identity to SEQ ID NO: 18, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with HIV spike protein, comprises an amino acid sequence having at least 40% sequence identity to SEQ ID NO: 18, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with HIV spike protein, comprises an amino acid sequence having at least 50% sequence identity to SEQ ID NO: 18, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with HIV spike protein, comprises an amino acid sequence having at least 60% sequence identity to SEQ ID NO: 18, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with HIV spike protein, comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO: 18, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with HIV spike protein, comprises an amino acid sequence having at least 75% sequence identity to SEQ ID NO: 18, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with HIV spike protein, comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 18, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with HIV spike protein, comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 18, or a fragment or functional derivative thereof.In some embodiments, the protein, e.g., a polypeptide that interacts with HIV spike protein, comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 18, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with HIV spike protein, comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 18, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with HIV spike protein, comprises, consists of, or consists essentially of SEQ ID NO: 18, or a fragment or functional derivative thereof.

[0195] In some embodiments, the protein, e.g., a polypeptide that interacts with Ebola virus glycoprotein, has at least 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 110%, 111%, 112%, 113%, 114%, 115%, 116%, 117%, 118%, 119%, 120%, 121%, 122%, 123%, 12 , 51%, 52%, 52%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity, or any value derivable therein.

[0196] In some embodiments, a protein, e.g., a polypeptide that interacts with an Ebola virus glycoprotein, comprises an amino acid sequence having at least 10% sequence identity to SEQ ID NO:20, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with an Ebola virus glycoprotein, comprises an amino acid sequence having at least 20% sequence identity to SEQ ID NO:20, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with an Ebola virus glycoprotein, comprises an amino acid sequence having at least 30% sequence identity to SEQ ID NO:20, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with an Ebola virus glycoprotein, comprises an amino acid sequence having at least 40% sequence identity to SEQ ID NO:20, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with an Ebola virus glycoprotein, comprises an amino acid sequence having at least 50% sequence identity to SEQ ID NO:20, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with the Ebola virus glycoprotein, comprises an amino acid sequence having at least 60% sequence identity to SEQ ID NO: 20, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with the Ebola virus glycoprotein, comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO: 20, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with the Ebola virus glycoprotein, comprises an amino acid sequence having at least 75% sequence identity to SEQ ID NO: 20, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with the Ebola virus glycoprotein, comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 20, or a fragment or functional derivative thereof.In some embodiments, the protein, e.g., a polypeptide that interacts with the Ebola virus glycoprotein, comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 20, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with the Ebola virus glycoprotein, comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 20, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with the Ebola virus glycoprotein, comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 20, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with the Ebola virus glycoprotein, comprises, consists of, or consists essentially of SEQ ID NO: 20, or a fragment or functional derivative thereof.

[0197] In some embodiments, a protein, e.g., a polypeptide that interacts with an influenza virus spike protein, has at least 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 110%, 111%, 120%, 122%, 123%, 124%, 125%, 126%, 127%, 128%, 129%, 130%, 131%, 132%, 133 , 50%, 51%, 52%, 52%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity, or any value derivable therein.

[0198] In some embodiments, a protein, e.g., a polypeptide that interacts with influenza virus spike protein, comprises an amino acid sequence having at least 10% sequence identity to SEQ ID NO:25, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with influenza virus spike protein, comprises an amino acid sequence having at least 20% sequence identity to SEQ ID NO:25, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with influenza virus spike protein, comprises an amino acid sequence having at least 30% sequence identity to SEQ ID NO:25, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with influenza virus spike protein, comprises an amino acid sequence having at least 40% sequence identity to SEQ ID NO:25, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with influenza virus spike protein, comprises an amino acid sequence having at least 50% sequence identity to SEQ ID NO:25, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with influenza virus spike protein, comprises an amino acid sequence having at least 60% sequence identity to SEQ ID NO: 25, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with influenza virus spike protein, comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO: 25, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with influenza virus spike protein, comprises an amino acid sequence having at least 75% sequence identity to SEQ ID NO: 25, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with influenza virus spike protein, comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 25, or a fragment or functional derivative thereof.In some embodiments, the protein, e.g., a polypeptide that interacts with influenza virus spike protein, comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 25, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with influenza virus spike protein, comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 25, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with influenza virus spike protein, comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 25, or a fragment or functional derivative thereof. In some embodiments, the protein, e.g., a polypeptide that interacts with influenza virus spike protein, comprises, consists of, or consists essentially of SEQ ID NO: 25, or a fragment or functional derivative thereof.

[0199] In some embodiments, a protein, e.g., a polypeptide that interacts with a RSV glycoprotein, has at least 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 110%, 111%, 112%, 113%, 114%, 115%, 116%, 117%, 118%, 119%, 120%, 121%, 122%, 123%, 124 and / or 100% sequence identity, or any value derivable therein.

[0200] In some embodiments, a protein, e.g., a polypeptide that interacts with a RSV glycoprotein, comprises an amino acid sequence having at least 10% sequence identity to SEQ ID NO: 34, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with a RSV glycoprotein, comprises an amino acid sequence having at least 20% sequence identity to SEQ ID NO: 34, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with a RSV glycoprotein, comprises an amino acid sequence having at least 30% sequence identity to SEQ ID NO: 34, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with a RSV glycoprotein, comprises an amino acid sequence having at least 40% sequence identity to SEQ ID NO: 34, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with a RSV glycoprotein, comprises an amino acid sequence having at least 50% sequence identity to SEQ ID NO: 34, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with a RSV glycoprotein, comprises an amino acid sequence having at least 60% sequence identity to SEQ ID NO: 34, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with a RSV glycoprotein, comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO: 34, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with a RSV glycoprotein, comprises an amino acid sequence having at least 75% sequence identity to SEQ ID NO: 34, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with a RSV glycoprotein, comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 34, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with a RSV glycoprotein, comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 34, or a fragment or functional derivative thereof.In some embodiments, a protein, e.g., a polypeptide that interacts with a RSV glycoprotein, comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 34, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with a RSV glycoprotein, comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 34, or a fragment or functional derivative thereof. In some embodiments, a protein, e.g., a polypeptide that interacts with a RSV glycoprotein, comprises, consists of, or consists essentially of SEQ ID NO: 34, or a fragment or functional derivative thereof.

[0201] In some embodiments, a polypeptide that interacts with a protein, e.g., a viral protein, further comprises a signal peptide sequence. A signal peptide (also called a signal sequence, targeting signal, localization signal, localization sequence, transit peptide, leader sequence, or leader peptide) is a short peptide (e.g., 16-30 amino acids in length) present at the N-terminus of a newly synthesized secretable protein. Signal peptides typically function to prompt the cell to translocate the protein to the cell membrane. In some embodiments, the signal peptide comprises an amino acid sequence having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NOs: 28-32, or a fragment or functional derivative thereof, or any value derivable therein.

[0202] In some embodiments, the signal peptide comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO:28, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 75% sequence identity to SEQ ID NO:28, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO:28, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:28, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:28, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO:28, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 99% sequence identity to SEQ ID NO:28, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises SEQ ID NO:28, or a fragment or functional derivative thereof.

[0203] In some embodiments, the nucleic acid sequence of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, or 16, or a fragment or functional derivative thereof, is at least 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 110%, 111%, 112%, 113%, 114%, 115%, 116%, 117%, 118%, 1 8%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 52%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82% , 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity, or any value derivable therein, to SEQ ID NO: 28 or a fragment or functional derivative thereof. The present invention further includes a signal peptide comprising an amino acid sequence with 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity, or any value derivable therein.

[0204] In some embodiments, the signal peptide comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO:29, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 75% sequence identity to SEQ ID NO:29, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO:29, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:29, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:29, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO:29, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 99% sequence identity to SEQ ID NO:29, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises SEQ ID NO:29, or a fragment or functional derivative thereof.

[0205] In some embodiments, the present invention relates to a method for the preparation of a compound having at least 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 110%, 111%, 112%, 113%, 114%, 115%, 116%, 117%, 118%, 119%, 120%, 121%, 122%, 123%, 124%, 125%, ,43%,44%,45%,46%,47%,48%,49%,50%,51%,52%,52%,54%,55%,56%,57%,58%,59%,60%,61%,62%,63%,64%,65%,66%,67%,68%,69%,70%,71%,72%,73%,74%,75%,76%,77%,78%,79%,80%,81%,82%,83%,84%,85% , 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity, or any value derivable therein, to SEQ ID NO: 29 or a fragment or functional derivative thereof, e.g., a polypeptide that interacts with the HIV spike protein. 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity, or any value derivable therein.

[0206] In some embodiments, the signal peptide comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO:30, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 75% sequence identity to SEQ ID NO:30, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO:30, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:30, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:30, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO:30, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 99% sequence identity to SEQ ID NO:30, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises SEQ ID NO:30, or a fragment or functional derivative thereof.

[0207] In some embodiments, the present invention relates to a method for the preparation of a compound having at least 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 110%, 111%, 112%, 113%, 114%, 115%, 116%, 117%, 118%, 119%, 120%, 121%, 122%, 123%, 124%, 125%, %,43%,44%,45%,46%,47%,48%,49%,50%,51%,52%,52%,54%,55%,56%,57%,58%,59%,60%,61%,62%,63%,64%,65%,66%,67%,68%,69%,70%,71%,72%,73%,74%,75%,76%,77%,78%,79%,80%,81%,82%,83%,84%,85%,86%,87%,88%,89 ...9%,80%,81%,82%,83%,84%,85%,86%,87%,88%,89%,89%,80%,81%,82%,83%,84%,89%,80%,81%,82%,83%,84%,85%,86%,87 Proteins, e.g., polypeptides that interact with the Ebola glycoprotein, that comprise an amino acid sequence having 5%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity, or any value derivable therein, with SEQ ID NO: 30 or a fragment or functional derivative thereof, have at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity, or any value derivable therein, with SEQ ID NO: 30 or a fragment or functional derivative thereof. , 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity, or any value derivable therein.

[0208] In some embodiments, the signal peptide comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO:31, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 75% sequence identity to SEQ ID NO:31, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO:31, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:31, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:31, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO:31, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 99% sequence identity to SEQ ID NO:31, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises SEQ ID NO:31, or a fragment or functional derivative thereof.

[0209] In some embodiments, the nucleotide sequence of SEQ ID NO: 25 or a fragment or functional derivative thereof is at least 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 110%, 111%, 112%, 113%, 114%, 115%, 116%, 117%, 118%, 119%, 120%, 121%, 122%, 123%, 124 3%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 52%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86% , 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity, or any value derivable therein, to SEQ ID NO: 31 or a fragment or functional derivative thereof, e.g., a polypeptide that interacts with the spike protein of influenza virus, Further included are signal peptides comprising an amino acid sequence with 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity, or any value derivable therein.

[0210] In some embodiments, the signal peptide comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO: 32, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 75% sequence identity to SEQ ID NO: 32, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 32, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 32, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 32, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 32, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises an amino acid sequence having at least 99% sequence identity to SEQ ID NO: 32, or a fragment or functional derivative thereof. In some embodiments, the signal peptide comprises SEQ ID NO: 32, or a fragment or functional derivative thereof.

[0211] In some embodiments, the present invention relates to a method for the preparation of a compound having at least 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 110%, 111%, 112%, 113%, 114%, 115%, 116%, 117%, 118%, 119%, 120%, 121%, 122%, 123%, 124%, 125%, %,43%,44%,45%,46%,47%,48%,49%,50%,51%,52%,52%,54%,55%,56%,57%,58%,59%,60%,61%,62%,63%,64%,65%,66%,67%,68%,69%,70%,71%,72%,73%,74%,75%,76%,77%,78%,79%,80%,81%,82%,83%,84%,85%,86%,87%,88%,89 ...9%,80%,81%,82%,83%,84%,85%,86%,87%,88%,89%,89%,80%,81%,82%,83%,84%,89%,80%,81%,82%,83%,84%,85%,86%,87 Proteins, e.g., polypeptides that interact with RSV glycoproteins, that contain an amino acid sequence having 5%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity, or any value derivable therein, have at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity, or any value derivable therein, with SEQ ID NO: 32 or a fragment or functional derivative thereof. , 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity, or any value derivable therein.

[0212] A. Polypeptides As used herein, "polypeptide," "peptide," or "protein" refers to a molecule comprising at least five amino acid residues. As used herein, the term "wild-type" refers to the endogenous version of a molecule that occurs naturally in an organism. In some embodiments, a wild-type version of a protein or polypeptide is used, while in many embodiments of the present disclosure, a modified protein or polypeptide is used. The above terms may be used interchangeably. A "modified protein" or "modified polypeptide" or "variant" refers to a protein or polypeptide whose chemical structure, particularly its amino acid sequence, has been altered relative to the wild-type protein or polypeptide. In some embodiments, a modified / variant protein or polypeptide has at least one modified activity or function (recognizing that a protein or polypeptide can have multiple activities or functions). It is specifically contemplated that a modified / variant protein or polypeptide may be altered with respect to one activity or function but still retain wild-type activity or function in other respects, such as immunogenicity.

[0213] As used herein, a "proteinaceous molecule," "proteinaceous composition," "proteinaceous compound," "proteinaceous chain," or "proteinaceous material" generally refers to, but is not limited to, a protein of more than about 30 amino acids, or a full-length endogenous sequence translated from a gene; a polypeptide of more than about 100 amino acids; and / or a peptide of about 30 to about 3000 amino acids. All of the above "proteinaceous" terms may be used interchangeably herein.

[0214] When a protein is specifically referred to herein, it generally refers to a native (wild-type) or recombinant (modified) protein, or, optionally, a protein with any signal sequence removed. A protein can be isolated directly from an organism in which it occurs naturally, produced by recombinant DNA / exogenous expression methods, or produced by solid-phase peptide synthesis (SPPS) or other in vitro methods. In certain embodiments, there are isolated nucleic acid segments and recombinant vectors incorporating nucleic acid sequences encoding a polypeptide (e.g., an antibody or fragment thereof). The term "recombinant" may be used in conjunction with a polypeptide or the name of a particular polypeptide, and generally refers to a polypeptide produced from a nucleic acid molecule that has been manipulated in vitro or is the product of replication of such a molecule.

[0215] In certain embodiments, the size of a protein or polypeptide (wild-type or modified) is 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 7, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 625, 650, 675, 700, 725, 750, 775, 800, 825, 850, 875, 900, 925, 950, 975, 1000, 1100, 1200, 1300, 1400, 1500, It is understood that polypeptides may include, but are not limited to, 1750, 2000, 2250, 2500, 2750, 3000, 3250, 3500, 3750, 4000, 4250, 4500, 4750, or 5000 amino acid residues or more, and any range derivable therein, or derivatives of the corresponding amino acid sequences described or referenced herein. It is contemplated that polypeptides may be mutated by truncation to be shorter than their corresponding wild-type forms, or may be altered by fusing or conjugating heterologous proteins or polypeptide sequences having specific functions (e.g., for targeting or localization, to enhance immunogenicity, for purification purposes, etc.). A protein may comprise one or more polypeptides.

[0216] As used herein, the term "domain" refers to any distinct functional or structural unit of a protein or polypeptide, generally a sequence of amino acids with a structure or function recognizable by those skilled in the art. For example, a domain may refer to an oligomerization domain of a protein or polypeptide. Collagen triple helix, coiled-coil, and other oligomerization domains mediate the assembly of multiple protein subunits. Oligomerization provides the functional advantages of multivalency and high binding strength, increased structural stability, and the combined functions of different domains. Domains, such as the oligomerization domains described herein, may be conserved. In evolutionary biology, conserved sequences are identical or similar sequences in nucleic acids (DNA and RNA) or proteins across species (orthologous sequences), or within genomes (paralogous sequences), or between donor and receptor taxa (heterologous sequences). Conservation indicates that a sequence has been maintained by natural selection. Highly conserved sequences are those that remain relatively unchanged up the phylogenetic tree.

[0217] In certain embodiments, the proteinaceous composition comprises at least one protein, polypeptide, or peptide. It is contemplated that virtually any protein-, polypeptide-, or peptide-containing component described herein may be used in the compositions and methods disclosed herein. In further embodiments, the proteinaceous composition comprises a biocompatible protein, polypeptide, or peptide. As used herein, the term "biocompatible" refers to a substance that does not produce significant adverse effects when applied or administered to a given organism according to the methods and amounts described herein. Such adverse or undesirable effects include effects such as significant toxicity or adverse immunological responses. In preferred embodiments, the biocompatible protein-, polypeptide-, or peptide-containing composition is generally a mammalian protein or peptide or a synthetic protein or peptide, each essentially free of toxins, pathogens, and harmful immunogens.

[0218] Proteinaceous compositions may be produced by any technique known to those skilled in the art, including expression of proteins, polypeptides or peptides by standard molecular biology techniques, isolation of proteinaceous compounds from natural sources, or chemical synthesis of proteinaceous material.

[0219] The nucleotide and protein, polypeptide, and peptide sequences of various genes have been previously disclosed and can be found in recognized computerized databases. Two commonly used databases are the National Center for Biotechnology Information's Genbank and GenPept databases (on the World Wide Web at ncbi.nlm.nih.gov / ) and The Universal Protein Resource (UniProt; on the World Wide Web at uniprot.org). The coding regions of these genes can be amplified and / or expressed using the techniques disclosed herein or as known to those skilled in the art.

[0220] In certain embodiments, a proteinaceous compound may be purified. Generally, "purified" refers to a particular or desired protein, polypeptide, or peptide composition that has been subjected to fractionation to remove various other proteins, polypeptides, or peptides, and which composition substantially retains its activity, as may be assessed, for example, by protein assays, as known to those of skill in the art for the particular or desired protein, polypeptide, or peptide.

[0221] Proteins and peptides suitable for use in the present invention may be self-proteins or peptides, although the present invention is clearly not limited to the use of such self-proteins. As used herein, the term "self-protein, polypeptide, or peptide" refers to a protein, polypeptide, or peptide derived from or obtained from an organism. Organisms that can be used include, but are not limited to, cattle, reptiles, amphibians, fish, rodents, birds, dogs, cats, fungi, plants, prokaryotes, viruses, or bacteriophages. A selected animal or human subject is preferred. Thus, a "self-protein, polypeptide, or peptide" can be used as a component of a composition intended for application to a selected animal or human subject.

[0222] It is contemplated that compositions of the present disclosure will have from about 0.001 mg to about 10 mg of total polypeptide, peptide, and / or protein per ml. The concentration of protein in the composition can be about, at least about, or at most about 0.001, 0.010, 0.050, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0 mg / ml or more (or any range derivable therein).

[0223] B. Nucleic acid In certain embodiments, nucleic acid sequences may be present in various instances, such as isolated segments of integrated sequences or recombinant polynucleotides and recombinant vectors encoding the polypeptides and / or derivatives, muteins, or variants thereof described herein; polynucleotides sufficient for use as hybridization probes; PCR or sequencing primers for identifying, analyzing, mutating, or amplifying polynucleotides encoding polypeptides; antisense nucleic acids for regulating expression of polynucleotides; and complementary sequences of the foregoing described herein. Nucleic acids encoding epitopes against which specific antibodies provided herein are provided are also provided. Nucleic acids encoding fusion proteins comprising these peptides are also provided. Nucleic acids may be single-stranded or double-stranded and may comprise RNA and / or DNA nucleotides, as well as artificial variants thereof (e.g., peptide nucleic acids).

[0224] The term "polynucleotide" refers to a nucleic acid molecule that is recombinant or isolated from total genomic nucleic acid. The term "polynucleotide" includes oligonucleotides (nucleic acids 100 residues or less in length) and recombinant vectors, including, for example, plasmids, cosmids, phages, viruses, and the like. Polynucleotides, in certain embodiments, contain regulatory sequences isolated substantially free from their naturally occurring gene or protein-coding sequences. Polynucleotides can be single-stranded (coding or antisense) or double-stranded, and can be RNA, DNA (genomic, cDNA, or synthetic), analogs thereof, or combinations thereof. Additional coding or non-coding sequences may or may not be present within a polynucleotide.

[0225] In this regard, the terms "gene," "polynucleotide," or "nucleic acid" are used to refer to a nucleic acid that encodes a protein, polypeptide, or peptide (including any sequences necessary for proper transcription, post-translational modification, or localization). As will be understood by those of skill in the art, this term encompasses genomic sequences, expression cassettes, cDNA sequences, and smaller engineered nucleic acid segments that express, or can be adapted to express, proteins, polypeptides, domains, peptides, fusion proteins, and mutants. A nucleic acid that encodes all or a portion of a polypeptide can contain a contiguous nucleic acid sequence that encodes all or a portion of such a polypeptide. It is also contemplated that a particular polypeptide can be encoded by a nucleic acid that includes variations having different nucleic acid sequences, but which nevertheless encode the same or a substantially similar protein.

[0226] In certain embodiments, polynucleotide variants having substantial identity to the sequences disclosed herein, e.g., at least 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, or more, when compared to the polynucleotide sequences provided herein using the methods described herein (e.g., BLAST analysis using standard parameters), are identified. , 46%, 47%, 48%, 49%, 50%, 51%, 52%, 52%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or higher sequence identity (including all values ​​and ranges therebetween).In certain embodiments, the isolated polynucleotide has at least 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 110%, 111%, 112%, 113%, 114%, 115%, 116%, 117%, 118%, 119%, 120%, 121%, 122%, 123%, 124%, 125%, 126%, 127%, or a nucleotide sequence encoding a polypeptide having 5%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the isolated polynucleotide. 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 110%, 111%, 120%, 122%, 130%, 140%, 141%, 142%, 143%, 144%, 150%, 151%, 152%, 153%, 154%, 155%, 156%, 157%, 158%, 159%, 200%, 201%, 202%, 203%, 204%, 205%, 206%, 207%, 208, 209, 210%, 211%, 212%, 213%, 214%, 215%, 216%, 217%, 218%, 219%, 220%, 221, 222, 230, Nucleotide sequences encoding polypeptides with 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity will result in polypeptides having a structure similar to that of the polypeptides described herein.

[0227] Regardless of the length of the coding sequence itself, a nucleic acid segment may be combined with other nucleic acid sequences, such as promoters, polyadenylation signals, additional restriction enzyme sites, multiple cloning sites, other coding segments, etc., and therefore its total length may vary considerably. Nucleic acids can be of any length. They can be, for example, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, 100, 125, 175, 200, 250, 300, 350, 400, 450, 500, 750, 1000, 1500, 3000, 5000, or more nucleotides in length, and / or can include one or more additional sequences, such as regulatory sequences, and / or can be part of a larger nucleic acid, such as a vector. Thus, it is contemplated that nucleic acid fragments of almost any length can be used, with the total length preferably being limited by the ease of preparation and use in the intended recombinant nucleic acid protocol. In some cases, the nucleic acid sequence may encode a polypeptide sequence with additional heterologous coding sequences, for example, to allow for purification, translocation, secretion, post-translational modification of the polypeptide, or for therapeutic benefits such as targeting or efficacy. As noted above, tags or other heterologous polypeptides can be added to the sequence encoding the modified polypeptide, and "heterologous" refers to a polypeptide that is not the same as the modified polypeptide.

[0228] Changes can be introduced by mutation into the nucleic acid, thereby resulting in a change in the amino acid sequence of the polypeptide it encodes. Mutations can be introduced using any technique known in the art. In one embodiment, one or more specific amino acid residues are altered, for example, using a site-directed mutagenesis protocol. In another embodiment, one or more randomly selected residues are altered, for example, using a random mutagenesis protocol. However, once created, the mutant polypeptide can be expressed and screened for desired properties.

[0229] Mutations can be introduced into a nucleic acid without significantly altering the biological activity of the polypeptide it encodes. For example, nucleotide substitutions can be made that result in amino acid substitutions at non-essential amino acid residues. Alternatively, one or more mutations can be introduced into a nucleic acid that selectively alters the biological activity of the polypeptide it encodes (see, for example, Romain Studer et al., Biochem. J. 449:581-594 (2013)). For example, mutations can quantitatively or qualitatively alter biological activity. Examples of quantitative changes include increasing, decreasing, or eliminating activity. Examples of qualitative changes include changing the antigen specificity of an antibody.

[0230] C. Variant Polypeptides Modifications and / or changes can be made to the proteins and / or polynucleotides encoding the proteins according to the invention while still obtaining molecules with similar or improved characteristics, and such biologically functional equivalents are also encompassed by the present invention.

[0231] Biologically functional equivalents may include polynucleotides that have been engineered to contain different sequences while simultaneously retaining the ability to encode a "wild-type" or standard protein or peptide or a "variant" protein or peptide. This can be achieved due to the degeneracy of the genetic code, i.e., the existence of multiple codons that encode the same amino acid.

[0232] With respect to functional equivalents, it will be appreciated by those skilled in the art that inherent in the protein and / or polynucleotide definition of a "biologically functional equivalent" is the concept that there are limits to the number of changes that can be made within a defined portion of the molecule while retaining the molecule with an acceptable level of equivalent biological activity. Thus, biologically functional equivalents are defined herein as proteins (and polynucleotides) with substitutions or mutations in selected amino acids (or codons) that retain, for example, the ability to interact with a target protein in vivo.

[0233] Generally, the shorter the length of a molecule, the fewer changes that can be made in the molecule while retaining function. Longer polypeptides can have an intermediate number of changes. Full-length proteins are most tolerant of a larger number of changes. However, it should be understood that certain molecules or domains that are highly dependent on their structure may tolerate little or no modification. In one example, a polynucleotide may be (and encode) a biologically functional equivalent with more significant changes. Certain amino acids can be substituted for other amino acids in a protein structure without appreciable loss of interactive binding ability with structures such as, for example, oligomerization domains, binding sites on substrate molecules, receptors, etc.

[0234] The following is a discussion of altering amino acids in proteins to create equivalent or even improved second-generation variant polypeptides or peptides. For example, certain amino acids can be substituted with other amino acids in a protein or polypeptide sequence, with or without appreciable loss of interactive binding ability with structures such as, for example, the antigen-binding region of an antibody or a binding site on a substrate molecule. Because the interacting ability and properties of a protein define its functional activity, specific amino acid substitutions can be made in a protein sequence and its corresponding DNA coding sequence, yet still produce a protein with similar or desirable properties. Thus, the inventors believe that various changes can be made to the DNA sequence of a gene encoding a protein without appreciable loss of its biological utility or activity.

[0235] The term "functionally equivalent codon" is used herein to refer to codons that encode the same amino acid, e.g., the six different codons for arginine. "Neutral substitutions" or "neutral mutations," which refer to changes in one or more codons that encode biologically equivalent amino acids, are also contemplated.

[0236] The amino acid sequence variants of the disclosure can be substitutional, insertional, or deletion variants. Variations in the polypeptides of the disclosure can affect 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or more non-contiguous or contiguous amino acids of the protein or polypeptide compared to the wild-type. A variant can comprise an amino acid sequence that is at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% identical (including all values ​​and ranges therebetween) to any sequence provided or referenced herein. A variant can contain 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more substituted amino acids.

[0237] It will also be understood that amino acid and nucleic acid sequences may include additional residues, such as additional N- or C-terminal amino acids, or 5' or 3' sequences, respectively, and still be essentially identical to one of the sequences disclosed herein, so long as the sequence meets the above criteria, including maintenance of the biological protein activity to which protein expression pertains. The addition of terminal sequences particularly applies to nucleic acid sequences, which may include, for example, various non-coding sequences adjacent to either the 5' or 3' portion of the coding region.

[0238] Deletion variants typically lack one or more residues of the native or wild-type protein. Individual residues can be deleted, or several consecutive amino acids can be deleted. A stop codon can be introduced (by substitution or insertion) into the encoding nucleic acid sequence to generate a truncated protein. For example, it is contemplated that a peptide can be mutated by truncation or deletion of several consecutive amino acids to make it shorter than the corresponding endogenous form.

[0239] Insertional mutants typically involve the addition of an amino acid residue at a non-terminal point in the polypeptide. This may involve the insertion of one or more amino acid residues. Terminal additions may also be generated, including fusion proteins, which are multimers or concatamers of one or more peptides or polypeptides described or referenced herein. For example, it is contemplated that peptides may be altered by fusing or conjugating heterologous protein or polypeptide sequences having a particular function (e.g., for targeting or localization, to enhance activity, for purification purposes, etc.).

[0240] Substitution variants typically involve exchanging one amino acid for another at one or more sites within a protein or polypeptide and can be designed to modulate one or more properties of the polypeptide, with or without the loss of other functions or properties. Substitutions can be conservative, i.e., one amino acid is replaced with one of similar chemical properties. A "conservative amino acid substitution" can involve the exchange of a member of one amino acid class for another member of the same class. Conservative substitutions are widely known in the art, and include, for example, alanine to serine; arginine to lysine; asparagine to glutamine or histidine; aspartic acid to glutamic acid; cysteine ​​to serine; glutamine to asparagine; glutamic acid to aspartic acid; glycine to proline; histidine to asparagine or glutamine; isoleucine to leucine or valine; leucine to valine or isoleucine; lysine to arginine; methionine to leucine or isoleucine; phenylalanine to tyrosine, leucine, or methionine; serine to threonine; threonine to serine; tryptophan to tyrosine; tyrosine to tryptophan or phenylalanine; and valine to isoleucine or leucine. Conservative amino acid substitutions can include non-naturally occurring amino acid residues, which are typically incorporated by chemical peptide synthesis rather than synthesis in biological systems. These include peptidomimetics or other reversed or inverted forms of amino acid moieties. Because the structural changes do not affect the ability of the protein to perform its designed function, so-called "conservative" changes do not destroy the biological activity of the protein. Accordingly, the inventors contemplate that various modifications can be made to the gene and protein sequences disclosed herein while still achieving the objectives of the invention.

[0241] Alternatively, substitutions can be "non-conservative" such that the function or activity of the polypeptide is affected. Non-conservative changes typically involve replacing an amino acid residue with a chemically different one, e.g., a non-polar or uncharged amino acid with a polar or charged amino acid, or vice versa. Non-conservative substitutions can involve exchanging a member of one amino acid class for a member of another class.

[0242] It will also be understood that amino acid and nucleic acid sequences may include additional residues, such as additional N- or C-terminal amino acids, or 5' or 3' sequences, respectively, and still be essentially as set forth in one of the sequences disclosed herein, so long as the sequence meets the above criteria, including maintenance of the biological protein activity to which protein expression pertains. The addition of terminal sequences particularly applies to nucleic acid sequences, which may include, for example, various non-coding sequences adjacent to either the 5' or 3' portion of the coding region.

[0243] The amino acid sequence variants of the present disclosure can be, for example, substitution, insertion, or deletion variants. A region or fragment of a polypeptide of the present disclosure can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, , 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 5, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 23 95, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254,255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296 , 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, ​​383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398 8, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, ​​383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 44 It is contemplated that the polypeptide may have an amino acid sequence with, at least, or at most 80, 381, 382, ​​383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400 or more amino acid substitutions, consecutive amino acid additions, or consecutive amino acid deletions. Alternatively, a region or fragment of a polypeptide of the present disclosure may be a fragment of any of SEQ ID NOs: 1-25, 27, 33, and 34, and at least or at most 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 121, 122, 131, 141, 142, 143, 144, 145, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99,It may have an amino acid sequence that comprises or consists of an amino acid sequence that is 100% (or any derivable range therein) identical.

[0244] Further, in some embodiments, the region or fragment is selected from the group consisting of positions 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 1 39, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 1 70, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201 1, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232 , 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263,264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 2 95, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326 6, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357 , 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, ​​383, 384, 385, 386, 387, 388, Starting at 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400 or more (position 1 is the N-terminus of the SEQ ID NO:), 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129 7, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121 , 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152,153、154、155、156、157、158、159、160、161、162、163、164、165、166、167、168、169、170、171、172、173、174、175、176、177、178、179、180、181、182、183、184、185、186、187、188、189、190、191、192、193、194、195、196、197、198、199、200、201、202、203、204、205、206、207、208、209、210、211、212、213、214、215、216、217、218、219、220、221、222、223、224、225、226、227、228、229、230、231、232、233、234、235、236、237、238、239、240、241、242、243、244、245、246、247、248、249、250、251、252、253、254、255、256、257、258、259、260、261、262、263、264、265、266、267、268、269、270、271、272、273、274、275、276、277、278、279、280、281、282、283、284、285、286、287、288、289、290、291、292、293、294、295、296、297、298、299、300、301、302、303、304、305、306、307、308、309、310、311、312、313、314、315、316、317、318、319、320、321、322、323、324、325、326、327、328、329、330、331、332、333、334、335、336、337、338、339、340、341、342、343、344、345、346、347、348、349、350、351、352、353、354、355、356、357、358、359、360、361、362、363、364、365、366、367、368、369、370、371、372、373、374、375、376、377、378、379、380、381、382、383、384、385、386、387、388、389、390、391、392、393、394、395、396、397、398、399、Polypeptides of the disclosure may comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 or more variant amino acids, or at least, or at most, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 or more variant amino acids of any of SEQ ID NOs: 1-25, 27, 33, and 34. 1, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195 4, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214,215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 30 0, 350, 400 or more consecutive amino acids, or any range derivable therein, and at least 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 110%, 111%, 112%, 113%, 114%, 115%, 116%, 117%, 118%, 119%, 120%, 121%, 122%, 123%, 3%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69% , 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% similar, identical, or homologous.

[0245] Polypeptides of the present disclosure include those having at least, at most, or exactly 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, , 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108 8, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139 , 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 2 02, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233 3, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264,265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300 , 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336 6, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, ​​383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 43 396, 397, 398, 399, or 400 substitutions (or any range derivable therein).

[0246] The substitutions are made at amino acid positions 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 5, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112 , 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 1 75, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 20 6, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237 , 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268,269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303 3, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, ​​383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 2, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, ​​383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, or 400 (or any navigable position therein).

[0247] Those skilled in the art can use well-known techniques to determine suitable variants of the polypeptides described herein. By targeting regions not believed to be important for activity, those skilled in the art can identify suitable regions of the molecule that can be altered without destroying activity. Those skilled in the art will also be able to identify amino acid residues and portions of molecules that are conserved between similar proteins or polypeptides. In further embodiments, regions that may be important for biological activity or structure can undergo conservative amino acid substitutions without significantly altering the biological activity or adversely affecting the protein or polypeptide structure.

[0248] In making such changes, the hydropathic index of amino acids may be taken into consideration. The hydropathic profile of a protein is calculated by assigning a numerical value (the "hydropathic index") to each amino acid and then iteratively averaging these values ​​along the peptide chain. Each amino acid is assigned a value based on its hydrophobicity and charge characteristics. They are as follows: isoleucine (+4.5); valine (+4.2); leucine (+3.8); phenylalanine (+2.8); cysteine / cysteine ​​(+2.5); methionine (+1.9); alanine (+1.8); glycine (-0.4); threonine (-0.7); serine (-0.8); tryptophan (-0.9); tyrosine (-1.3); proline (1.6); histidine (-3.2); glutamic acid (-3.5); glutamine (-3.5); aspartic acid (-3.5); asparagine (-3.5); lysine (-3.9); and arginine (-4.5). The importance of the hydrophobic amino acid index in conferring interactive biological function on a protein is generally understood in the art (Kyte et al., J. Mol. Biol. 157:105-131 (1982)). It is recognized that the relative hydropathic properties of amino acids contribute to the secondary structure of the resulting protein or polypeptide, which in turn determines the interaction of the protein or polypeptide with other molecules, such as enzymes, substrates, receptors, DNA, antibodies, antigens, etc. It is also known that certain amino acids may be substituted for other amino acids having a similar hydropathic index or score and still retain similar biological activity. When making changes based on hydropathic index, certain embodiments include substitution of amino acids whose hydropathic index is within ±2. In some aspects of the present disclosure, this includes within ±1, and in other aspects of the present disclosure, this includes within ±0.5.

[0249] It is also understood in the art that similar amino acid substitutions can be effectively made based on hydrophilicity.US Patent No. 4,554,101, incorporated herein by reference, states that the greatest local average hydrophilicity of a protein, as governed by the hydrophilicity of adjacent amino acids, correlates with the biological properties of the protein.In certain embodiments, the greatest local average hydrophilicity of a protein, as governed by the hydrophilicity of adjacent amino acids, correlates with its immunogenicity, i.e., the biological properties of the protein. These amino acid residues have been assigned the following hydrophilicity values: arginine (+3.0); lysine (+3.0); aspartic acid (+3.0±1); glutamic acid (+3.0±1); serine (+0.3); asparagine (+0.2); glutamine (+0.2); glycine (0); threonine (-0.4); proline (-0.5±1); alanine (-0.5); histidine (-0.5); cysteine ​​(-1.0); methionine (-1.3); valine (-1.5); leucine (-1.8); isoleucine (-1.8); tyrosine (-2.3); phenylalanine (-2.5); and tryptophan (-3.4). When making changes based on similar hydrophilicity values, certain embodiments include substitutions of amino acids whose hydrophilicity values ​​are within ±2, other embodiments include those within ±1, and still other embodiments include those within ±0.5. In some instances, epitopes can also be identified from primary amino acid sequences based on hydrophilicity. These regions are also called "epitope core regions." It is understood that an amino acid can be substituted for another with a similar hydrophilicity value and still produce a biologically equivalent and immunologically equivalent protein.

[0250] Furthermore, one skilled in the art can review structure-function studies that identify residues in similar polypeptides or proteins that are important for activity or structure. In light of such comparisons, one can predict the importance of amino acid residues in a protein that correspond to amino acid residues in the similar protein that are important for activity or structure. One skilled in the art can select chemically similar amino acid substitutions for such predicted important amino acid residues.

[0251] Those skilled in the art can also analyze the three-dimensional structure and amino acid sequence relative to that structure in similar proteins or polypeptides. Taking such information into account, those skilled in the art can predict the alignment of amino acid residues of a polypeptide relative to its three-dimensional structure. Those skilled in the art may choose not to alter amino acid residues predicted to be on the surface of the protein because such residues may be involved in important interactions with other molecules. Furthermore, those skilled in the art can generate and test variants containing single amino acid substitutions at each desired amino acid residue. These variants can then be screened using standard assays for binding and / or activity, thus obtaining information gathered from such routine experiments that may enable those skilled in the art to determine amino acid positions where further substitutions should be avoided, either alone or in combination with other mutations. Various tools available for determining secondary structure can be found on the World Wide Web at expasy.org / proteomics / protein_structure.

[0252] In some embodiments of the present disclosure, amino acid substitutions are made to (1) reduce susceptibility to proteolysis, (2) reduce susceptibility to oxidation, (3) alter binding affinity for forming protein complexes, (4) alter binding affinity for a ligand or antigen, and / or (5) confer or modify other physicochemical or functional properties to such polypeptides. For example, single or multiple amino acid substitutions (in certain embodiments, conservative amino acid substitutions) can be made in a naturally occurring sequence. Substitutions can be made in portions of the protein outside the domain(s) that form intermolecular contacts. In such embodiments, conservative amino acid substitutions can be used that do not substantially alter the structural features of the protein or polypeptide (e.g., one or more substituted amino acids that do not disrupt the secondary structure that characterizes the native protein).

[0253] As used herein, "amino molecule" refers to any amino acid, amino acid derivative, or amino acid mimetic known to those skilled in the art. In certain embodiments, the residues of a proteinaceous molecule are contiguous, and no non-amino molecules interrupt the sequence of amino molecule residues. In other embodiments, the sequence may include one or more non-amino molecule moieties. In certain embodiments, the sequence of residues of a proteinaceous molecule may be interrupted by one or more non-amino molecule moieties. Peptides and polypeptides include the 20 "natural" amino acids and their post-translational modifications. However, in vitro peptide synthesis allows for the use of modified and / or unusual amino acids.

[0254] Thus, the term "proteinaceous composition" encompasses amino acid sequences that contain at least one of the 20 common amino acids in naturally synthesized proteins, or at least one modified or unusual amino acid, including but not limited to those shown in the table below. [Table 1]

[0255] In addition to the biologically functional equivalents described above, the inventors also contemplate that structurally similar compounds may be formulated to mimic significant portions of the peptides or polypeptides of the invention. Such compounds, which may be referred to as peptidomimetics, may be used in the same manner as the peptides of the invention and are therefore also functional equivalents.

[0256] Specific mimetics that mimic elements of protein secondary and tertiary structure are described in Johnson et al. (1993). The underlying rationale behind the use of peptidomimetics is that the peptide backbone of a protein exists primarily to orient amino acid side chains to facilitate molecular interactions, such as those of antibodies and / or antigens. Thus, peptidomimetics are designed to enable molecular interactions similar to those of natural molecules.

[0257] Some successful applications of the peptidomimetic concept have focused on mimicking β-turns in proteins, which are known to be highly antigenic. Potential β-turn structures in polypeptides can be predicted by computer-based algorithms, as discussed herein. Once the constituent amino acids of the turn are determined, mimetics can be constructed to achieve a similar spatial orientation of the essential amino acid side chain elements.

[0258] Another approach focuses on the use of small, multidisulfide-containing proteins as attractive structural templates for generating biologically active conformations that mimic the binding sites of larger proteins (Vita et al., 1998). A structural motif that appears to be evolutionarily conserved in certain toxins is small (30–40 amino acids), stable, and highly tolerant to mutations. This motif consists of a beta sheet and an alpha helix bridged to an inner core by three disulfides.

[0259] A beta II turn has been successfully mimicked in Weisshoff et al. (1999) using a cyclic L-pentapeptide and one with D-amino acids, and Johannesson et al. (1999) reported a bicyclic tripeptide with reverse turn-inducing properties.

[0260] Methods for generating specific structures have been disclosed in the art. For example, alpha-helix mimetics are disclosed in U.S. Patent Nos. 5,446,128; 5,710,245; 5,840,833; and 5,859,184. These structures make peptides or proteins more thermally stable and more resistant to proteolysis.

[0261] Methods for generating conformationally restricted beta turns and beta bulges are described, for example, in U.S. Patent Nos. 5,440,013; 5,618,914; and 5,670,155. Beta turns allow for varied side substituents without corresponding changes in the main chain conformation and have suitable termini for incorporation into peptides by standard synthetic procedures. Other types of mimetic turns include reverse and gamma turns. Reverse turn mimetics are disclosed in U.S. Patent Nos. 5,475,085 and 5,929,237, and gamma turn mimetics are described in U.S. Patent Nos. 5,672,681 and 5,674,976.

[0262] II. Exogenous Delivery of Protein-Interacting Polypeptides In some aspects, there are nucleic acid molecules encoding the polypeptides of the present disclosure. In certain embodiments, nucleic acid vectors can be constructed to contain exogenous nucleic acid sequences that enable cells to express the proteinaceous compositions and polypeptides disclosed herein. Details of the components and delivery methods of these vectors are disclosed below.

[0263] In various embodiments, DNA constructs or vectors are provided that encode the polypeptide sequences disclosed herein. Genetic modifications can also be introduced into cells. These modifications include, for example, transducing cells with vectors encoding the polypeptides to generate cells that express the polypeptides.

[0264] Cells according to the present disclosure include any cell containing the proteinaceous compositions and polypeptide sequences disclosed herein. DNA constructs or vectors constructed to contain exogenous nucleic acid sequences that enable cells to express the proteinaceous compositions and polypeptide sequences disclosed herein can be introduced and expressed as described herein. It should be understood that the basic concepts of the present disclosure described herein are not limited by cell type. Cells according to the present disclosure include prokaryotic cells, eukaryotic cells, mammalian cells, animal cells, human cells, etc. Furthermore, cells include any in which it is beneficial or desirable to modulate the production of functional proteins.

[0265] A. Vector In some embodiments, expression of the polypeptide sequences disclosed herein is achieved by operably linking a nucleic acid encoding the polypeptide sequence or a portion thereof to a promoter and incorporating the construct into an expression vector that is taken up and expressed by a cell. The vector may be suitable for replication and, in some cases, integration in eukaryotes. Typical cloning vectors contain transcription and translation terminators, initiation sequences, and a promoter useful for regulating expression of the desired nucleic acid sequence. For example, nucleic acids can be cloned into vectors including, but not limited to, plasmids, phagemids, phage derivatives, animal viruses, and cosmids. Vectors of particular interest include expression vectors, replication vectors, probe generation vectors, and sequencing vectors. In general, suitable vectors contain an origin of replication functional in at least one organism, a promoter sequence, convenient restriction endonuclease sites, and one or more selectable markers (see, e.g., WO 01 / 96584; WO 01 / 29058; and U.S. Pat. No. 6,326,193). In some embodiments, a suitable vector is capable of crossing the blood-brain barrier.

[0266] In certain embodiments, the expression vector can be provided to cells in the form of a non-viral vector. For example, the non-viral vector can include a minicircle vector. Minicircles are a newly developed type of DNA carrier for gene therapy. The main advantages of minicircles include a cleaner genetic background with minimal viral or bacterial genetic elements and sustained high-level protein expression, and the small size of minicircles can enable their use in aerosols for drug delivery. The non-viral vector can include the pcDNA3.1(+) vector. The non-viral vector may comprise a nucleotide sequence having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO:26, or any value derivable therein.

[0267] In certain embodiments, the expression vector may be provided to the cell in the form of a viral vector. Viral vector technology is widely known in the art and is described, for example, in Sambrook et al. (2001) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York, and other virology and molecular biology manuals.

[0268] Several virus-based systems have been developed for gene transfer into mammalian cells. Viruses useful as vectors include, but are not limited to, retroviruses, adenoviruses, adeno-associated viruses, herpesviruses, and lentiviruses (including self-inactivating lentiviral vectors). For example, adenoviruses provide a convenient platform for gene delivery systems. A selected gene can be inserted into a vector and packaged into retroviral particles using techniques known in the art. The recombinant virus can then be isolated and delivered to cells of interest either in vivo or ex vivo. Thus, in some embodiments, a nucleic acid encoding a polypeptide sequence is introduced into cells using a recombinant vector (e.g., a viral vector including a lentivirus, retrovirus, gamma-retrovirus, adeno-associated virus (AAV), herpesvirus, or adenovirus).

[0269] Vectors can also contain other components or functionalities that further regulate gene delivery and / or gene expression or that otherwise provide beneficial properties to target cells. Such other components include, for example, components that affect cell binding or targeting (including components that mediate cell-type or tissue-specific binding), components that affect uptake of vector nucleic acid by cells, components that affect localization of the polynucleotide within the cell after uptake (such as agents that mediate nuclear localization), and components that affect expression of the polynucleotide.

[0270] Such components may also include markers, such as detectable and / or selectable markers that can be used to detect or select cells that have taken up and are expressing the nucleic acid delivered by the vector. Such components may be provided as natural features of the vector (such as the use of certain viral vectors that have components or functionality that mediate binding and uptake), or the vector may be modified to provide such functionality. A wide variety of such vectors are known in the art and are generally available. Where a vector is maintained in a host cell, the vector may be stably replicated by the cell during mitosis as an autonomous structure, may be integrated into the genome of the host cell, or may be maintained in the nucleus or cytoplasm of the host cell.

[0271] The eukaryotic expression cassette contained in the vector contains, inter alia, (5' to 3') regulatory elements including a eukaryotic transcription promoter operably linked to a protein coding sequence, splice signals including intervening sequences, transcription termination / polyadenylation sequences, post-transcriptional regulatory elements, and an origin of replication.

[0272] 1. Promoter / Enhancer A "promoter" is a regulatory sequence, which is a region of a nucleic acid sequence at which the initiation and rate of transcription are controlled. It can include genetic elements to which regulatory proteins and molecules, such as RNA polymerase and other transcription factors, can bind to initiate specific transcription of a nucleic acid sequence. The phrases "operably positioned," "operably linked," "under control," and "under transcriptional control" mean that the promoter is in the correct functional location and / or orientation relative to a nucleic acid sequence to control transcription initiation and / or expression of that sequence.

[0273] Promoters generally contain sequences that function to position the start site for RNA synthesis. The most well-known example of this is the TATA box, but in some promoters lacking a TATA box, such as the promoters of the mammalian terminal deoxynucleotidyl transferase gene and the SV40 late genes, separate elements surrounding the start site itself help to anchor the location of initiation. Additional promoter elements regulate the frequency of transcription initiation. Typically, these are located in the region 30–110 bp upstream of the start site, but some promoters have been shown to contain functional elements downstream of the start site as well. To place a coding sequence "under the control" of a promoter, the 5' end of the transcription start site of the transcriptional reading frame is positioned "downstream" (i.e., 3') of the selected promoter. The "upstream" promoter stimulates transcription of DNA and promotes expression of the encoded RNA.

[0274] The spacing between promoter elements is often flexible, so that promoter function is preserved when elements are inverted or moved relative to one another. For example, in the thymidine kinase promoter, the spacing between promoter elements can be increased by up to 50 bp before activity begins to decline. Depending on the promoter, individual elements appear to be able to function cooperatively or independently to activate transcription. Promoters may or may not be used in conjunction with "enhancers," which refer to cis-acting regulatory sequences involved in the transcriptional activation of nucleic acid sequences.

[0275] A promoter can be one naturally associated with a nucleic acid sequence, as can be obtained by isolating the 5' non-coding sequences located upstream of a coding segment and / or exon. Such a promoter can be referred to as "endogenous." Similarly, an enhancer can be one naturally associated with a nucleic acid sequence located either downstream or upstream of that sequence. Alternatively, certain advantages can be obtained by placing a coding nucleic acid segment under the control of a recombinant or heterologous promoter, which refers to a promoter not normally associated with a nucleic acid sequence in its natural environment. A recombinant or heterologous enhancer also refers to an enhancer not normally associated with a nucleic acid sequence in its natural environment. Such promoters or enhancers can include promoters or enhancers of other genes, as well as promoters or enhancers isolated from any other virus or prokaryotic or eukaryotic cell, and promoters or enhancers that are "non-naturally occurring," i.e., contain different elements of different transcriptional regulatory regions and / or mutations that alter expression. In addition to producing promoter and enhancer nucleic acid sequences synthetically, the sequences may be produced using recombinant cloning and / or nucleic acid amplification techniques, including PCR™, in connection with the compositions disclosed herein (see U.S. Pat. Nos. 4,683,202 and 5,928,906, which are specifically incorporated by reference herein in their entireties). Furthermore, it is contemplated that control sequences that direct transcription and / or expression of sequences in non-nuclear organelles, such as mitochondria, may similarly be used.

[0276] Naturally, it will be important to use a promoter and / or enhancer that effectively directs expression of the DNA segment in the organelle, cell type, tissue, organ, or organism chosen for expression. Those skilled in the art of molecular biology are generally aware of the use of promoter, enhancer, and cell type combinations for protein expression (see, e.g., Sambrook et al., 1989, specifically incorporated herein by reference in its entirety). The promoter used may be constitutive, cell-specific, tissue-specific, inducible, and / or useful under appropriate conditions for directing high-level expression of the introduced DNA segment, such as is advantageous in large-scale production of recombinant proteins and / or peptides. The promoter may be heterologous or endogenous.

[0277] Additionally, any promoter / enhancer combination (e.g., according to the Eukaryotic Promoter Data Base EPDB, available on the World Wide Web at epd.isb-sib.ch / ) can be used to drive expression. Non-limiting examples of other potential promoters include early or late viral promoters, such as the SV40 early or late promoter, the cytomegalovirus (CMV) immediate-early promoter, and the Rous sarcoma virus (RSV) early promoter; eukaryotic promoters, such as the β-actin promoter (Ng, 1989; Quitsche et al., 1989), the GADPH promoter (Alexander et al., 1988, Ercolani et al., 1988), and the metallothionein promoter (Karin et al., 1989; Richards et al., 1984); and linked response element promoters, such as the cyclic AMP response element promoter (cre), serum response element promoter (sre), phorbol ester promoter (TPA), and the TATA box-near minimal response element promoter (tre). It is also possible to use the human growth hormone promoter sequence (e.g., the human growth hormone minimal promoter described in Genbank, accession number X05244, nucleotides 283-341) or the mouse mammary tumor promoter (available from ATCC catalog number ATCC 45007). A specific example would be the phosphoglycerate kinase (PGK) promoter.

[0278] In some embodiments, expression of the polynucleotide is regulated by a constitutive promoter, hi some embodiments, the constitutive promoter is CAG (also known as CAGGS or CBA), EF-1ALPHA, ubiquitin, or CMV.

[0279] In some embodiments, expression of the polynucleotide is regulated by a cell-specific promoter. In some embodiments, the cell-specific promoter is a neuron-specific promoter. In some embodiments, the neuron-specific promoter comprises a human synapsin I (SYN) promoter, a mouse calcium / calmodulin-dependent protein kinase II (CaMKII) promoter, a rat tubulin alpha I (Ta1), a rat neuron-specific enolase (NSE) promoter, a human platelet-derived growth factor beta chain (PDGF) promoter, or a THY1 (CD90) promoter. In some embodiments, the cell-specific promoter is human synapsin I.

[0280] In some embodiments, expression of the polynucleotide is regulated by a tissue-specific promoter. In some embodiments, the tissue-specific promoter is a choroid plexus-specific promoter. In some embodiments, the choroid plexus-specific promoter comprises a Prlr promoter, a Spint2 promoter, or an F5 promoter. In some embodiments, the tissue-specific promoter is a liver-specific promoter. Liver-specific promoters are described, for example, in L.M. Kattenhorn et al., Hum. Gene Ther. 27(12):947-961 (2016), the entire contents of which are specifically incorporated herein by reference.

[0281] 2. Protease cleavage site / self-cleaving peptide and internal ribosome binding site Suitable protease cleavage sites and self-cleaving peptides are known to those skilled in the art (see, for example, Ryan et al., 1997; Scymczak et al., 2004). Examples of protease cleavage sites include furin protease, potyvirus NIa protease (e.g., tobacco etch virus protease), potyvirus HC protease, potyvirus P1 (P35) protease, biovirus Nla protease, biovirus RNA-2-encoded protease, aphthovirus L protease, enterovirus 2A protease, rhinovirus 2A protease, picorna 3C protease, comovirus 24K protease, nepovirus 24K protease, RTSV (rice globular virus) 3C-like protease, PY\IF (parsnip yellow mottle virus) 3C-like protease, thrombin, factor Xa, and enterokinase cleavage sites. Due to its high cleavage stringency, the TEV (tobacco etch virus) protease cleavage site may be used. In some embodiments, the protease cleavage site is a cleavage site for a furin protease.

[0282] Exemplary self-cleaving peptides (also called "cis-acting hydrolytic elements," CHYSEL; see deFelipe (2002)) are derived from potyvirus and cardiovirus 2A peptides. Specific self-cleaving peptides can be selected from 2A peptides derived from FMDV (foot-and-mouth disease virus), equine rhinitis A virus, Tosea asigna virus, and porcine teschovirus.

[0283] Specific initiation signals can also be used for efficient translation of coding sequences in polycistronic messages. These signals include the ATG start codon or adjacent sequences. For example, the initiation signal can include the Kozak consensus sequence, which has an amino acid sequence containing GCCACCAUGGG. See Kozak, 1987; Harte et al., 2012. It may be necessary to provide exogenous translational control signals, including the ATG start codon. One of skill in the art would be readily able to determine this and provide the necessary signals. It is well known that to ensure translation of the entire insert, the initiation codon must be "in-frame" with the reading frame of the desired coding sequence. Exogenous translational control signals and initiation codons can be either natural or synthetic. The efficiency of expression can be enhanced by including appropriate transcriptional enhancer elements.

[0284] In certain embodiments, the use of internal ribosome entry site (IRES) elements is used to generate multigene or polycistronic messages. IRES elements can bypass the ribosome scanning model of 5' methylated Cap-dependent translation and initiate translation at internal sites (Pelletier and Sonenberg, 1988). IRES elements from two members of the picornavirus family (polio and encephalomyocarditis) have been described (Pelletier and Sonenberg, 1988), and IRESs from mammalian messages have also been described (Macejak and Sarnow, 1991). IRES elements can be linked to heterologous open reading frames. Multiple open reading frames can be transcribed together, each separated by an IRES, creating a polycistronic message. Thanks to the IRES element, each open reading frame is accessible to ribosomes for efficient translation. Multiple genes can be efficiently expressed using a single promoter / enhancer to transcribe a single message (see U.S. Pat. Nos. 5,925,565 and 5,935,819, each of which is incorporated herein by reference).

[0285] 3. Multiple Cloning Site A vector can contain a multiple cloning site (MCS), a nucleic acid region containing multiple restriction enzyme sites, any of which can be used in conjunction with standard recombinant techniques to digest the vector (see Carbonelli et al., 1999, Levenson et al., 1998, and Cocea, 1997, which are specifically incorporated by reference in their entireties). "Restriction enzyme digestion" refers to the catalytic cleavage of a nucleic acid molecule by an enzyme that functions only at specific locations within the nucleic acid molecule. Many of these restriction enzymes are commercially available. The use of such enzymes is widely understood by those skilled in the art. Often, vectors are linearized or fragmented using restriction enzymes that cut within the MCS to allow exogenous sequences to be ligated into the vector. "Ligation" refers to the process of forming phosphodiester bonds between two nucleic acid fragments that may or may not be contiguous with each other. Techniques involving restriction enzymes and ligation reactions are well known to those skilled in the art of recombinant technology.

[0286] 4. Splicing site Most transcribed eukaryotic RNA molecules undergo RNA splicing to remove introns from the primary transcript. Vectors containing genomic eukaryotic sequences may require donor and / or acceptor splice sites to ensure proper processing of the transcript for protein expression (see, e.g., Chandler et al., 1997, incorporated herein by reference).

[0287] 5. Termination Signal A vector or construct may contain at least one termination signal. A "termination signal" or "terminator" consists of a DNA sequence involved in specific termination of RNA transcription by an RNA polymerase. Thus, in certain embodiments, a termination signal that ends the production of an RNA transcript is contemplated. A terminator may be necessary in vivo to achieve a desired message level.

[0288] In eukaryotic systems, the terminator region may also contain specific DNA sequences that allow for site-specific cleavage of the new transcript to expose a polyadenylation site. This signals a specialized endogenous polymerase to add a stretch of approximately 200 A residues (polyA) to the 3' end of the transcript. RNA molecules modified with this polyA tail appear to be more stable and are translated more efficiently. Thus, in other embodiments, including eukaryotic organisms, the terminator contains a signal for RNA cleavage, and the terminator signal promotes polyadenylation of the message. Terminator and / or polyadenylation site elements may help increase message levels and minimize readthrough from the cassette to other sequences.

[0289] Contemplated terminators include any known transcription terminator described herein or known to one of skill in the art, including, but not limited to, for example, a gene termination sequence, such as the bovine growth hormone terminator, or a viral termination sequence, such as the SV40 terminator. In certain embodiments, the termination signal can be a transcribable or lack of a transcribable sequence, such as by truncation of the sequence.

[0290] 6. Polyadenylation Signal In expression, particularly in eukaryotic expression, a polyadenylation signal is typically included to ensure proper polyadenylation of the transcript. The nature of the polyadenylation signal is not believed to be critical to successful implementation, and any such sequence may be used. Exemplary embodiments include the SV40 polyadenylation signal or the bovine growth hormone polyadenylation signal, which are advantageous and known to function well in various target cells. Polyadenylation may increase the stability of the transcript or facilitate cytoplasmic transport.

[0291] 7. Post-transcriptional regulatory elements Vectors for use in the present disclosure may also include one or more post-transcriptional regulatory elements (PRE). Examples of PREs include the woodchuck hepatitis virus PRE (WPRE), the hepatitis B virus PRE, and intron A of the human cytomegalovirus immediate early gene. For further examples and details, see Sun et al. (2009) and Mariati et al. (2010). In certain embodiments, the PRE is a WPRE. The WPRE is a DNA sequence that, when transcribed, creates a tertiary structure to enhance expression of the gene delivered by the viral vector.

[0292] 8. Origin of replication To propagate a vector in a host cell, the vector may contain one or more origin of replication sites (often referred to as "ori"), such as a nucleic acid sequence corresponding to the EBV oriP described above, or a genetically engineered oriP with a similar or enhanced function in differentiation programming, which is a specific nucleic acid sequence at which replication is initiated. Alternatively, the replication origin or autonomously replicating sequence (ARS) of the other extrachromosomally replicating viruses described above can be used.

[0293] B. Vector Delivery Genetic modification or introduction of exogenous nucleic acid into cells can use any suitable method for nucleic acid delivery for cell transformation, as described herein or known to those skilled in the art. Methods for introducing and expressing genes into cells are known in the art. In relation to expression vectors, the vectors can be easily introduced into host cells, such as mammalian, bacterial, yeast, or insect cells, by any method known in the art. For example, expression vectors can be transferred into host cells by physical, chemical, or biological means.

[0294] Such methods include direct delivery of DNA by ex vivo transfection (Wilson et al., 1989; Nabel et al., 1989, etc.); transduction; viral transduction; injection (U.S. Pat. No. 5,994,624; U.S. Pat. No. 5,789,215, each of which is incorporated herein by reference), including microinjection (Harland and Weintraub, 1985; U.S. Pat. No. 5,789,215, each of which is incorporated herein by reference). Nos. 5,981,274, 5,945,100, 5,780,448, 5,736,524, 5,702,932, 5,656,610, 5,589,466, and 5,580,859); electroporation (U.S. Pat. No. 5,384,253, incorporated herein by reference; Tur-Kaspa et al. (1986); Potter et al. (1984)); calcium phosphate precipitation (Graham and Van Der Eb (1973); Chen and Okayama (1987); Rippe et al. (1990); the use of DEAE-dextran followed by polyethylene glycol (Gopal (1985)); direct sonic loading (Fechheimer et al. (1987)); nucleofection; lipofection or liposome-mediated transfection (Nicolau and Sene (1982); Fraley et al. (1979); Nicolau et al. (1987); Wong et al. (1980); Kaneda et al. (1989); Kato et al. (1991)) and receptor-mediated transfection (Wu and Wu (1987); Wu and Wu (1988)); microprojectile or nanoparticle bombardment (PCT Application No. WO 94 / 09699 and 95 / 06128; U.S. Patent Nos. 5,610,042; 5,322,783 5,563,055; 5,550,318; 5,538,877; and 5,538,880 (each of which is incorporated by reference herein); agitation using silicon carbide fibers (Kaeppler et al. (1990); U.S. Patent Nos. 5,302,523 and 5,464,765 (each of which is incorporated by reference herein)); Agrobacterium-mediated transformation (U.S. Patent Nos. 5,591,616 and 5,563,055, each of which is incorporated by reference herein);These include, but are not limited to, PEG-mediated transformation of protoplasts (Omirulleh et al., 1993; U.S. Patent Nos. 4,684,611 and 4,952,500, each incorporated herein by reference); desiccation / inhibition-mediated DNA uptake (Potrykus et al., 1985); heat shock (Froger and Hall, 2007); and any combination of such methods. By application of techniques such as these, organelle(s), cell(s), tissue(s) or organism(s) may be stably or transiently transformed;

[0295] Physical methods for introducing polynucleotides into host cells include calcium phosphate precipitation, lipofection, particle bombardment, microinjection, electroporation, etc. Methods for producing cells containing vectors and / or exogenous nucleic acids are widely known in the art (see, e.g., Sambrook et al. (2001) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York).

[0296] Biological methods for introducing a polynucleotide of interest into a host cell can include the use of DNA and RNA vectors into which the polynucleotide of interest or transgene can be inserted. Viral vectors have become the most widely used method for inserting genes into mammalian, e.g., human, cells. Other viral vectors can be derived from lentiviruses, poxviruses, herpes simplex virus I, adenoviruses, adeno-associated viruses, and the like (see, e.g., U.S. Patent Nos. 5,350,674 and 5,585,362).

[0297] Chemical means for introducing polynucleotides into host cells include colloidal dispersion systems such as macromolecular complexes, nanocapsules, microspheres, beads, and lipid-based systems including oil-in-water emulsions, micelles, mixed micelles, and liposomes. Nanoparticles are also contemplated. An exemplary colloidal system for use as a delivery vehicle in vitro and in vivo is a liposome (e.g., artificial membrane vesicle).

[0298] For example, methods for gene therapy and methods for delivering genes to a subject using adeno-associated viruses are described in US 6,967,018, WO2014 / 093622, US 2008 / 0175845, US 2014 / 0100265, EP2432490, EP2352823, EP2384200, WO2014 / 127198, WO2005 / 122723, WO2008 / 137490, WO2013 / 1421 14, WO2006 / 128190, WO2009 / 134681, EP2341068, WO2008 / 027084, WO2009 / 054994, WO2014059031, US No. 7,977,049 and WO 2014 / 059029, each of which is specifically incorporated herein by reference in its entirety.

[0299] 1. Liposome-mediated Transfection One exemplary delivery vehicle is a lipid and / or liposome. The use of lipid formulations is contemplated for the introduction of nucleic acids into host cells (in vitro, ex vivo, or in vivo). In another embodiment, the nucleic acid may be associated with a lipid. The lipid-associated nucleic acid may be encapsulated in the aqueous interior of the liposome, interspersed within the lipid bilayer of the liposome, attached to the liposome via a linking molecule associated with both the liposome and the oligonucleotide, entrapped in the liposome, complexed with the liposome, dispersed in a solution containing lipid, mixed with lipid, combined with lipid, contained in a suspension in lipid, contained in or complexed with a micelle, or otherwise associated with lipid. Lipid-, lipid / DNA-, or lipid / expression vector-associated compositions are not limited to any particular structure in solution. For example, they may exist in a bilayer structure, as micelles, or in a "collapsed" structure. They may also simply be dispersed in solution, and sometimes form aggregates that are not uniform in size or shape.Lipid is a fatty substance that can be naturally occurring lipid or synthetic lipid.For example, lipid includes the lipid droplets that naturally occur in cytoplasm, and the class of compounds that contain long-chain aliphatic hydrocarbons and their derivatives, such as fatty acids, alcohols, amines, amino alcohols, and aldehydes.

[0300] In certain embodiments, nucleic acids can be entrapped in lipid complexes, such as liposomes. Liposomes are vesicular structures characterized by a phospholipid bilayer membrane and an internal aqueous medium. Multilamellar liposomes have multiple lipid layers separated by aqueous medium. They form spontaneously when phospholipids are suspended in an excess of aqueous solution. The lipid components undergo self-rearrangement before the formation of a closed structure, trapping water and dissolved solutes between the lipid bilayers (Ghosh and Bachhawat, 1991). The amount of liposomes used can vary depending on the nature of the liposomes and the cells used; for example, about 5 to about 20 μg of vector DNA per 1 to 10 million cells can be contemplated.

[0301] Liposome-mediated nucleic acid delivery and expression of foreign DNA in vitro has been very successful (Nicolau and Sene, 1982; Fraley et al., 1979; Nicolau et al., 1987). The feasibility of liposome-mediated delivery and expression of foreign DNA in cultured chick embryo, HeLa, and hepatoma cells has also been demonstrated (Wong et al., 1980).

[0302] In certain embodiments, liposomes can be complexed with hemagglutinating virus (HVJ), which has been shown to promote fusion with cell membranes and facilitate cell entry of liposome-encapsulated DNA (Kaneda et al., 1989). In other embodiments, liposomes can be complexed with or used in conjunction with nuclear non-histone chromosomal protein 1 (HMG-1) (Kato et al., 1991). In yet further embodiments, liposomes can be complexed with or used in combination with both HVJ and HMG-1. In other embodiments, the delivery vehicle can comprise a ligand and a liposome.

[0303] In various embodiments, lipids suitable for use can be obtained from commercial sources. For example, Lipofectamine can be obtained from Thermo Fisher Scientific, Waltham, Mass. Dimyristyl phosphatidylcholine ("DMPC") can be obtained from Sigma, St. Louis, Mo. Dicetyl phosphate ("DCP") can be obtained from K&K Laboratories (Plainview, NY). Cholesterol ("Choi") can be obtained from Calbiochem-Behring. Dimyristyl phosphatidylglycerol ("DMPG") and other lipids can be obtained from Avanti Polar Lipids, Inc. (Birmingham, Ala.) Stock solutions of lipids in chloroform or chloroform / methanol can be stored at approximately -20°C. Chloroform evaporates more readily than methanol and can therefore be used as the sole solvent. "Liposome" is a generic term encompassing a variety of unilamellar and multilamellar lipid vesicles formed by the formation of enclosed lipid bilayers or aggregates. Liposomes can be characterized as vesicular structures with a phospholipid bilayer membrane and an internal aqueous medium. Multilamellar liposomes have multiple lipid layers separated by aqueous medium. They form spontaneously when phospholipids are suspended in an excess of aqueous solution. The lipid components undergo self-rearrangement before the formation of a closed structure, trapping water and dissolved solutes between the lipid bilayers (Ghosh et al. (1991) Glycobiology 5:505-510). However, compositions with structures in solution that differ from the typical vesicular structure are also encompassed. For example, lipids may adopt a micellar structure or simply exist as heterogeneous aggregates of lipid molecules. Lipofectamine-nucleic acid complexes are also contemplated.

[0304] 2. Electroporation In certain embodiments, nucleic acids are introduced into cells by electroporation, which involves exposing a suspension of cells and DNA to a high-voltage discharge. Recipient cells can be made susceptible to transformation by mechanical wounding. The amount of vector used can also vary depending on the nature of the cells used; for example, about 5 to about 20 μg of vector DNA per 1 to 10 million cells can be contemplated.

[0305] Transfection of eukaryotic cells using electroporation has been very successful: mouse pre-B lymphocytes have been transfected with the human kappa immunoglobulin gene (Potter et al., 1984) and rat hepatocytes with the chloramphenicol acetyltransferase gene (Tur-Kaspa et al., 1986).

[0306] 3. Calcium phosphate In another embodiment, calcium phosphate precipitation is used to introduce nucleic acids into cells. Human KB cells were transfected with adenovirus 5 DNA (Graham and Van Der Eb, 1973) using this technique. Mouse L (A9), mouse C127, CHO, CV-1, BHK, NIH3T3, and HeLa cells were also transfected in this manner with the neomycin marker gene (Chen and Okayama, 1987), and rat hepatocytes were transfected with various marker genes (Rippe et al., 1990).

[0307] 4.DEAE-dextran In another embodiment, DEAE-dextran followed by polyethylene glycol is used to deliver nucleic acids into cells. In this manner, reporter plasmids have been introduced into mouse myeloma and erythroleukemia cells (Gopal, 1985).

[0308] C. Selectable or Screenable Markers Regardless of the method used to introduce exogenous nucleic acid into host cells or otherwise expose cells to inhibitors of the present disclosure, various assays can be performed to confirm the presence of the recombinant DNA sequence in the host cells. Such assays include, for example, "molecular biological" assays well known to those skilled in the art, such as Southern and Northern blotting, RT-PCR, and PCR; "biochemical" assays, such as detecting the presence or absence of specific peptides by immunological means (ELISA and Western blot), or by the assays described herein to identify agents within the scope of the present disclosure.

[0309] In certain embodiments, cells containing exogenous nucleic acid can be identified in vitro or in vivo by including a marker in the expression vector or exogenous nucleic acid. Such a marker would confer an identifiable change to the cells that allows for easy identification of cells containing the expression vector. Generally, a selectable marker can confer a characteristic that allows for selection. A positive selectable marker can be one whose presence allows for its selection, while a negative selectable marker is one whose presence prevents its selection. An example of a positive selectable marker is a drug resistance marker.

[0310] In addition to markers that confer a phenotype that allows for the identification of transformants based on the implementation of conditions, other types of markers are contemplated, including screening markers based on colorimetric analysis, such as GFP. Alternatively, screenable enzymes such as herpes simplex virus thymidine kinase (tk) or chloramphenicol acetyltransferase (CAT) may be utilized as negative selection markers. Those skilled in the art will likely also know how to use immunological markers in conjunction with FACS analysis. The marker used is not considered important, so long as it can be expressed simultaneously with the nucleic acid encoding the gene product. Further examples of selection and screening markers are well known to those skilled in the art.

[0311] Selectable markers can include the type of reporter genes used in laboratory microbiology, molecular biology, and genetic engineering to indicate the success of transfection or other procedures intended to introduce foreign DNA into cells. Selectable markers are often antibiotic resistance genes; cells that have undergone a procedure to introduce foreign DNA are grown on a medium containing the antibiotic, and cells that are able to grow have successfully taken up and expressed the introduced genetic material. Examples of selectable markers include the Abicr gene from Tn5, which confers antibiotic resistance to geneticin, or the Neo gene.

[0312] Screening markers may include reporter genes, allowing researchers to distinguish between desired and undesired cells. Certain embodiments of the present invention utilize reporter genes to indicate specific cell lineages. For example, r...

Claims

1. 1. A composition for use in a method for modulating a target protein or a biological function thereof in vivo in a subject comprising contacting the target protein or a portion thereof and / or a native interaction partner of the target protein or a portion thereof with a composition comprising an effective amount of a polypeptide having an amino acid sequence corresponding to a sequence of the target protein, wherein the length of the polypeptide is greater than 30 amino acids, comprising: wherein the polypeptide and the target protein form a non-native protein complex by contact of the target protein with the polypeptide, thereby regulating the target protein or its biological function in vivo; a native interaction partner of the target protein and the polypeptide form a non-native protein complex upon contact of the native interaction partner of the target protein with the polypeptide, thereby regulating the target protein or its biological function in vivo; and / or the polypeptide, the target protein, and the native interaction partner of the target protein form a non-native protein complex upon contact of the target protein and the native interaction partner of the target protein with the polypeptide, thereby regulating the target protein or its biological function in vivo; Optionally, the polypeptide has an amino acid sequence corresponding to an oligomerization domain of a target protein; and the polypeptide oligomerizes with an oligomerization domain of a target protein to form a non-native protein complex, thereby regulating the target protein or its biological function in vivo; the polypeptide oligomerizes with an oligomerization domain of a native interaction partner of the target protein to form a non-native protein complex, thereby regulating the target protein or its biological function in vivo; and / or The polypeptide oligomerizes with the oligomerization domain of the target protein and the native interaction partner of the target protein to form a non-native protein complex, thereby regulating the target protein or its biological function in vivo.

2. 2. The composition of claim 1, wherein the polypeptide having an amino acid sequence corresponding to the sequence of the target protein has at least 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99% identity to the sequence of the target protein or comprises the corresponding sequence of the target protein.

3. 3. The composition of claim 1 or 2, wherein the target protein is a viral protein, optionally wherein the target protein is a viral glycoprotein and / or a viral spike protein.

4. 4. The composition of any one of claims 1 to 3, wherein modulating a target protein or its biological function in vivo treats or prevents a disease or condition in a subject, and optionally the disease or condition is a viral infection.

5. A composition according to any one of claims 1 to 4, wherein Non-native protein complexes undergo proteasomal degradation; The formation of the non-native protein complex regulates the target protein or its biological function in vivo by inhibiting homo-oligomerization of the target protein; The formation of the non-native protein complex regulates the target protein or its biological function in vivo by inhibiting hetero-oligomerization of the target protein; and / or The composition, wherein the formation of the non-native protein complex regulates the target protein or its biological function in vivo by inhibiting homo- and hetero-oligomerization of the target protein.

6. A composition for treating or preventing an infectious disease in a subject, comprising a polypeptide having an amino acid sequence corresponding to the sequence of a target protein and / or a native interaction partner of the target protein, optionally wherein the sequence of the target protein is an oligomerization domain of the target protein and has at least 10% identity with SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 25, or 34 of the Sequence Listing, and wherein the polypeptide contacts the target protein and / or the native interaction partner of the target protein to form a non-native protein complex.

7. 7. The composition of claim 6, Where: Non-native protein complexes undergo proteasomal degradation; Treating or preventing infection by regulating a target protein or its biological function in vivo; The formation and translocation of a target protein to the cell surface and / or viral envelope of a subject is inhibited; and / or the amount of the target protein on the cell surface and / or viral envelope of the subject is reduced; composition.

8. 8. The composition of claim 6 or 7, comprising: wherein the infectious disease is a coronavirus infection, and the coronavirus comprises SARS-CoV, and the protein comprises a SARS-CoV spike protein; the coronavirus comprises SARS-CoV-2 and the protein comprises the SARS-CoV-2 spike protein; the coronavirus comprises MERS-CoV and the protein comprises a MERS-CoV spike protein; the coronavirus comprises HCoV-229E and the protein comprises HCoV-229E spike protein; the coronavirus comprises HCoV-NL63 and the protein comprises HCoV-NL63 spike protein; the coronavirus comprises HCoV-OC43 and the protein comprises the HCoV-OC43 spike protein; or the coronavirus comprises HCoV-HKU1 and the protein comprises HCoV-HKU1 spike protein; the infection is an HIV infection and the protein comprises an HIV spike protein, optionally the HIV spike protein comprises an HIV gp160 spike protein; the infectious disease is an Ebola infection and the protein comprises an Ebola glycoprotein, optionally the Ebola glycoprotein comprises an Ebola GP glycoprotein; the infection is an influenza infection; and The influenza comprises influenza virus A and the protein comprises influenza virus A spike protein; the influenza virus comprises influenza virus A / H1 and the protein comprises influenza virus A / H1 HA spike protein; Influenza virus A includes influenza virus A / H3 and the protein includes influenza virus A / H3 HA spike protein; The influenza comprises influenza virus B and the protein comprises influenza virus B spike protein; the influenza virus B comprises influenza virus B / Victoria and the protein comprises influenza virus B / Victoria HA spike protein; or the influenza virus B comprises influenza virus B / Yamagata and the protein comprises an influenza virus B / Yamagata HA spike protein; or the infection is an RSV infection, and the protein comprises an RSV glycoprotein, and optionally the RSV glycoprotein comprises an RSV F glycoprotein; composition.

9. The composition according to any one of claims 6 to 8, the infection is a coronavirus infection and the polypeptide has at least 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to or comprises SEQ ID NO:2 of the Sequence Listing, SEQ ID NO:4 of the Sequence Listing, SEQ ID NO:6 of the Sequence Listing, SEQ ID NO:8 of the Sequence Listing, SEQ ID NO:10 of the Sequence Listing, SEQ ID NO:12 of the Sequence Listing, SEQ ID NO:14 of the Sequence Listing, or SEQ ID NO:16 of the Sequence Listing; the infection is an HIV infection and the polypeptide has at least 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to or comprises the sequence of SEQ ID NO:18 of the Sequence Listing; the infectious disease is an Ebola infectious disease, and the polypeptide has at least 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to or comprises the sequence of SEQ ID NO: 20 in the sequence listing; the infection is an influenza infection and the polypeptide has at least 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to or comprises the sequence of SEQ ID NO:25 in the sequence listing; The infection is an RSV infection, and the polypeptide has at least 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to SEQ ID NO: 34 in the sequence listing, or comprises the sequence of SEQ ID NO: 34 in the sequence listing; composition.

10. A composition according to any one of claims 6 to 9, comprising: The subject is diagnosed with an infectious disease; The subject is diagnosed with symptoms of an infectious disease; or The subject is diagnosed as being at risk for an infectious disease. composition.

11. 11. The composition of any one of claims 6 to 10, wherein a subject is at high risk of having an infectious disease, does not have an infectious disease, is negative for an infectious disease, and / or is diagnosed as having an infectious disease, and optionally the infectious disease is prevented, the severity is reduced, and / or the onset is delayed.

12. 12. The composition of any one of claims 6-11, wherein the subject is provided with an effective amount of a second therapy against the infection, optionally the second therapy comprising an antibiotic, an antiviral, a convalescent serum, an immunomodulator, an anticoagulant, a fluid, oxygen, a corticosteroid, an antibody, GSnP-6, a sialyl Lewis X analog, an antiproliferative agent, a calcineurin inhibitor, an anti-signaling compound, or a combination thereof.

13. The composition according to any one of claims 1 to 12, wherein a dose of between 0.1-1000 mg / kg or 0.1-1000 μg / kg body weight of said polypeptide is administered to the subject; or The polypeptide is expressed from a vector encoding the polypeptide, and 1×10 ８ ~1×10 １８ a dose of vector copies / kg of the subject's body weight is administered to the subject, the vector transduces cells of the subject, and the cells of the subject express the polypeptide; composition.

14. 14. The composition of any one of claims 1 to 13, further comprising a pharma- ceutically acceptable carrier, optionally wherein the pharma- ceutically acceptable carrier comprises a liposome, a polymeric micelle, a microsphere, or a nanoparticle.

15. The composition according to any one of claims 1 to 14, The composition may be administered in a single dose or in multiple doses; The composition is delivered to the subject once a day, more than once a day, more than once a week, more than once a month, or more than once a year; The composition is delivered systemically or locally; and / or The composition is administered to a subject intranasally, intravenously, intraperitoneally, intratracheally, intramuscularly, endoscopically, transdermally, subcutaneously, topically, intracranially, by inhalation, injection, infusion, or perfusion; composition.

16. a pharmaceutical composition comprising a polypeptide or a vector encoding a polypeptide having an amino acid sequence corresponding to the sequence of a target protein and / or a native interaction partner of the target protein, optionally wherein the sequence of said target protein is an oligomerization domain of the target protein; wherein the length of the polypeptide is greater than 30 amino acids; and wherein the polypeptide has at least 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99% identity to or comprises the sequence of the target protein.

17. The pharmaceutical composition of claim 16, wherein the vector encodes a polypeptide comprising an amino acid sequence having 10, 15, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 25, or 34 in the sequence listing, or encodes a polypeptide comprising amino acids comprising the sequence of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 25, or 34 in the sequence listing.

18. 18. The composition of claim 16 or 17, further combined with a second therapy for the infection, optionally comprising an antibiotic, an antiviral, convalescent serum, an immunomodulator, an anticoagulant, fluids, oxygen, a corticosteroid, an antibody, GSnP-6, a sialyl Lewis X analog, an antiproliferative agent, a calcineurin inhibitor, an anti-signaling compound, or a combination thereof.

19. 19. The composition of any one of claims 16 to 18, wherein the composition further comprises a pharma- ceutically acceptable carrier, optionally wherein the pharma- ceutically acceptable carrier comprises a liposome, a polymeric micelle, a microsphere, or a nanoparticle.

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