WO2021081515A2

WO2021081515A2 - Compositions and methods for the treatment of human immunodeficiency virus

Info

Publication number: WO2021081515A2
Application number: PCT/US2020/057394
Authority: WO
Inventors: Suzanne AKERS-RODRIGUEZ; Leslie W. Tari
Original assignee: Cidara Therapeutics, Inc.
Priority date: 2019-10-25
Filing date: 2020-10-26
Publication date: 2021-04-29
Also published as: WO2021081515A3

Abstract

This disclosure relates to fusion proteins, conjugates, compositions, methods for inhibiting viral growth, and methods for the treatment of viral infections (e.g., HIV infections). In particular, the invention features fusion proteins which include at least one peptide that binds to HIV glycoprotein 41 (gp41) and at least one Fc domain monomer.

Description

COMPOSITIONS AND METHODS FOR THE TREATMENT OF HUMAN IMMUNODEFICIENCY VIRUS Background The need for novel antiviral treatments for human immunodeficiency virus (HIV) is significant and especially critical in the medical field. Since the first case of HIV was identified over 30 years ago, 78 million people have become infected with HIV and 35 million have died from acquired immune deficiency syndrome (AIDS)-related illnesses. Currently, 36.9 million people worldwide are living with HIV or AIDS, including 1.8 million children under the age of 15. An estimated 1.8 million individuals worldwide became newly infected with HIV in 2017. The development of antiviral treatments for HIV has been a continuing challenge. Since the first U.S. FDA approved anti-HIV drugs in 1987, a series of antiretroviral therapies have been developed. However, drug-resistant strains have emerged limiting the number of patients that can use these anti- retroviral therapies. HIV antiviral inhibitors come in many several classes targeting distinct steps of the HIV cycle. One class of antivirals, nucleoside reverse transcriptase inhibitors inhibit viral replication by chain termination after being incorporated into growing DNA strands by HIV reverse transcriptase. Another class, non-nucleoside reverse transcription inhibitors, similarly target reverse transcription, however at a different site than nucleoside reverse transcription inhibitors. A different class of antivirals, integrase inhibitors, inhibit viral DNA insertion into the host cellular genome. Protease inhibitors are agents that inhibit the protease enzyme, a key enzyme in the assembly of new virus particles. One class of antivirals, known as viral entry inhibitors, contains agents that interfere in viral entry into the cell by binding to HIV envelope (Env) glycoprotein. Viral entry inhibitors target, for example, the surface subunit gp120 receptor of the HIV virus or the associated transmembrane protein, gp41. Gp41 is coded with gp120 as one gp160 by the env gene of HIV. Gp160 is then extensively glycosylated and proteolytically cleaved by furin, a host cellular protease. The high glycosylation of the env coded glycoproteins allows them to escape the human body's immune system. In contrast to gp120, however, gp41 is less glycosylated and more conserved (less prone to genetic variations). Once gp160 has been cleaved into its individual subunits, the subunits are then associated non-covalently on the surface of the viral envelope. Gp41 and gp120, when non-covalently bound to each other, are referred to as the envelope spike complex and are formed as a heterotrimer of three gp41 and three gp120. These complexes found on the surface of HIV are responsible for the attachment, fusion, and ultimately the infection of host cells. While gp120 sits on the surface of the viral envelope, gp41 is the transmembrane portion of the spike complex with a portion of the glycoprotein buried within the viral envelope at all times. Many of the known antiviral agents are secreted or cleared by the kidney, requiring dose adjustments in those with compromised kidney function, and they have drug-drug interactions that may increase the effect of adverse reactions, particularly in HIV positive individuals undergoing organ transplant. Furthermore, many of these agents have been shown to be directly nephrotoxic, inducing a variety of kidney disorders. New, more effective therapies for treating HIV are needed. Summary The disclosure relates to fusion proteins, conjugates, compositions, methods for inhibiting viral growth, and methods for the treatment of viral infections. In particular, the invention features fusion proteins which include at least one peptide that binds to HIV glycoprotein 41 (gp41) and at least one Fc domain monomer. The Fc domain monomer of each of two fusions proteins may dimerize to form an Fc domain, where each monomer of the Fc domain is conjugated to at least on gp41-binding peptide. HIV binds to the host CD4 cell receptor via the viral protein gp120. Upon binding to gp 120, viral transmembrane protein gp140 undergoes a conformational change that assists in the fusion of the viral membrane to the host cell membrane. Accordingly, the gp41-binding peptide of the fusion proteins described herein prevents viral attachment fusion and entry into the host immune cell. The Fc monomers or Fc domains in the conjugates bind to FcγRs (e.g., FcRn, FcγRI, FcγRIIa, FcγRIIc, FcγRIIIa, and FcγRIIIb) on immune cells, e.g., neutrophils, to activate phagocytosis and effector functions, such as antibody-dependent cell-mediated cytotoxicity (ADCC), thus leading to the engulfment and destruction of viral particles by immune cells and further enhancing the antiviral activity. Such compositions are useful in methods for the inhibition of viral growth and in methods for the treatment of viral infections, such as those caused by an HIV-1 and HIV-2. In a first aspect, the invention features a fusion protein comprising an Fc domain monomer conjugated to at least one gp41-binding peptide. In some embodiments, the fusion protein includes one Fc domain monomer conjugated (e.g., covalently conjugated by a linker) to one gp41-binding peptide. In some embodiments, the fusion protein includes one Fc domain monomer conjugated to two gp41-binding peptides. In some embodiments, the fusion protein includes the structure: (P₂-L₂)_n2-B-(L₁-P₁)_n1 wherein B is an Fc domain monomer; P₁ and P₂ are each independently a gp41-binding peptide; L₁ and L₂ are each independently a linker; and n₁ and n₂ are each independently 0 or 1, wherein at least one of n₁ and n₂ is 1. In some embodiments, n₁ is 1, n₂ is 0, and the fusion protein comprises the structure: B-L₁-P₁. In some embodiments, the linker (L₁) is conjugated to C-terminus of the Fc domain monomer (B) and to the N-terminus of the gp41-binding peptide (P₁). In other embodiments, the linker (L₁) is conjugated to N-terminus of the Fc domain monomer (B) and to the C-terminus of the gp41-binding peptide (P₁). In other embodiments, the linker (L₁) is conjugated to N-terminus of the Fc domain monomer (B) and to the N-terminus of the gp41-binding peptide (P₁). In other embodiments, the linker (L₁) is conjugated to C-terminus of the Fc domain monomer (B) and to the C-terminus of the gp41-binding peptide (P₁). In some embodiments, n₁ is 1, n₂ is 1, and the fusion protein comprises the structure: P₂-L₂-B-L₁- P₁. In some embodiments, the linker (L₂) is conjugated to the C-terminus of the gp41-binding peptide (P₂) and to the N-terminus of the Fc domain monomer (B), and the linker (L₁) is conjugated to the C- terminus of the Fc domain monomer (B) and to the N-terminus of the gp41-binding peptide (P₁). In some embodiments, the linker (L₂) is conjugated to the N-terminus of the gp41-binding peptide (P₂) and to the N-terminus of the Fc domain monomer (B), and the linker (L₁) is conjugated to the N-terminus of the gp41-binding peptide (P₁) and to the C-terminus of the Fc domain monomer (B). In some embodiments, the linker (L₂) is conjugated to the C-terminus of the gp41-binding peptide (P₂) and to the N-terminus of the Fc domain monomer (B), and the linker (L₁) is conjugated to the C-terminus of the gp41-binding peptide (P₁) and to the C-terminus of the Fc domain monomer (B). In some embodiments, L₁ and/or L₂ are each an independently selected peptide linker comprising between 2 and 200 amino acids (e.g., 2-10 amino acids, 10-30 amino acids, 30-50 amino acids, 50-100 amino acids, or 100-200 amino acids). In some embodiments, L₁ and/or L₂ are each an independently selected peptide linker comprising between 5 and 25 amino acids. In some embodiments, L₁ and L₂ are each an independently selected peptide linker comprising the amino acid sequence of any one of (GS)x, (GGS)x, (GGGGS)x, (GGSG)x, (SGGG)x, wherein x is an integer from 1 to 50 (e.g., 1 to 20, 1 to 10, or 1 to 5). In some embodiments, B, L₁, and P₁ are expressed as a single polypeptide chain. In some embodiments, B, L₂, and P₂ are expressed as a single polypeptide chain. In some embodiments, P₂, L₂, B, L₁, and P₁ are expressed together as a single polypeptide chain. In some embodiments, L₁ includes a chemical linker that is covalently conjugated to each of B and P₁. In some embodiments, L₂ includes a chemical linker that is covalently conjugates to each of B and L₂. In some embodiments, L₁ includes a chemical linker that is covalently conjugated to each of B and P₁ and L₂ includes a chemical linker that is covalently conjugates to each of B and L₂. In some embodiments, B and P₁ are expressed as separate polypeptide chains and are subsequently each covalently conjugated to L₁. In some embodiments, B and P₂ are expressed as separate polypeptide chains and are subsequently each covalently conjugated to L₂. In some embodiments, P₂, B, and P₁ are expressed as separate polypeptide chains, P₂ and B are subsequently each covalently conjugated to L₂, and P₁ and B are subsequently each covalently conjugated to L₁. In some embodiments, P₁ and P₂ are each an independently selected gp41-binding peptide comprising an amino acid sequence having at least 85% sequence identity (e.g., at least 90%, 95%, 98%, or 99% sequence identity) to an amino acid selected from any one of SEQ ID NOs.75-85 In some embodiments, P₁ and P₂ are each an independently selected gp41-binding peptide including an amino acid sequence selected from any one of SEQ ID NOs.75-85. In some embodiments, B is an Fc domain monomer comprising an amino acid sequence that shares at least 85% sequence identity (e.g., at least 90%, 95%, 98%, or 99% sequence identity) with an amino acid sequence selected from any one of SEQ ID NOs.1-77 and 133-193. In some embodiments, B is an Fc domain monomer including an amino acid sequence selected from any one of SEQ ID NOs.1- 77 and 133-193. In some embodiments, the fusion protein is a fusion protein of Table 1. Table 1. Fusion proteins

In some embodiments, the fusion protein is a fusion protein of Table 1, wherein the linker (L₁) is a chemical linker or a peptide linker. In preferred embodiments of Table 1, L₁ is a peptide linker, such as a peptide linker having 2-100 amino acid residues, such as any peptide linker described herein. In some embodiments, the peptide linker has the formula (G4S)x, where x is an integer from 1 to 10. In some embodiments, the fusion protein is a fusion protein of Table 2. Table 2. Fusion proteins

In some embodiments, the fusion protein includes an amino acid sequence that shares at least 85% sequence identity (e.g., at least 90%, 95%, 98%, or 99% sequence identity) with an amino acid sequence selected from any one of the fusion proteins of Table 2. In some embodiments, the fusion protein includes an Fc domain having the sequences of SEQ ID NO: 63, SEQ ID NO: 64. SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO:76, or SEQ ID NO: 77. For example, the fusion protein is a fusion protein of Table 1 or Table 2. The Fc domain; the C-terminal Lys residue of the Fc domain (e.g., the C-terminal Lys residue of SEQ ID NO: 63, SEQ ID NO: 64. SEQ ID NO: 67, or SEQ ID NO: 68) may be present or absent. In some embodiments, the fusion protein (e.g., a fusion protein of Table 1 or 2) includes an Fc domain having at least 85% sequence identity (e.g., at least 90%, 95%, 98%, or 99% sequence identity) with the amino acid sequence of any one of SEQ ID NO: 63, SEQ ID NO: 64. SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO:76, or SEQ ID NO: 77. In some embodiments, the fusion protein (e.g., a fusion protein of Table 1 or 2) includes a Gp41 binding peptide having at least 85% sequence identity (e.g., at least 90%, 95%, 98%, or 99% sequence identity) with the amino acid sequence of any one of SEQ ID NO: 90, SEQ ID NO: 91, or SEQ ID NO: 94. In another aspect, the invention features a conjugate including a first fusion protein selected from any of the gp41 binding peptide-Fc domain monomer fusion proteins described herein; and a second fusion protein selected from any of the gp41 binding peptide-Fc domain monomer fusion proteins described herein; wherein the Fc domain monomer (B) of the first fusion protein and the Fc domain monomer (B) of the second fusion protein dimerize to form an Fc domain. In some embodiments, the first fusion protein and the second fusion protein have the same structure and the conjugate is a homodimer. In another aspect, the invention features a conjugate including a first fusion protein of Table 1 and a second fusion protein of Table 1, wherein the Fc domain monomer (B) of the first fusion protein and the Fc domain monomer (B) of the second fusion protein dimerize to form an Fc domain. In preferred embodiments, the dimer is a homodimer. In another aspect, the invention features a conjugate including a first fusion protein of Table 2 and a second fusion protein of Table 2, wherein the Fc domain monomer (B) of the first fusion protein and the Fc domain monomer (B) of the second fusion protein dimerize to form an Fc domain. In preferred embodiments, the dimer is a homodimer. In another aspect, the invention provides a pharmaceutical composition comprising any of the fusion proteins or conjugates described herein, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. In another aspect, the invention provides a method for the treatment of a subject having a viral infection or presumed to have a viral infection, the method comprising administering to the subject an effective amount of any of the fusion proteins, conjugates, or compositions described herein. In another aspect, the invention provides a method for the prophylactic treatment of a viral infection in a subject in need thereof, the method comprising administering to the subject an effective amount of any of the fusion proteins, conjugates, or compositions described herein. In some embodiments, the viral infection is caused by HIV. In some embodiments, the viral infection is HIV-1 or HIV-2. In some embodiments, the subject is immunocompromised. In some embodiments, the subject has been diagnosed with humoral immune deficiency, T cell deficiency, neutropenia, asplenia, or complement deficiency. In some embodiments, the subject is being treated or is about to be treated with an immunosuppressive therapy. In some embodiments, the subject has been diagnosed with a disease which causes immunosuppression. In some embodiments, the disease is cancer or acquired immunodeficiency syndrome. In some embodiments, the cancer is leukemia, lymphoma, or multiple myeloma. In some embodiments, the subject has undergone or is about to undergo hematopoietic stem cell transplantation. In some embodiments, wherein the subject has undergone or is about to undergo an organ transplant. In some embodiments, the fusion protein or composition is administered intramuscularly, intravenously, intradermally, intraarterially, intraperitoneally, intralesionally, intracranially, intraarticularly, intraprostatically, intrapleurally, intratracheally, intranasally, intravitreally, intravaginally, intrarectally, topically, intratumorally, peritoneally, subcutaneously, subconjunctival, intravesicularlly, mucosally, intrapericardially, intraumbilically, intraocularally, orally, locally, by inhalation, by injection, or by infusion. In some embodiments, the subject is treated with a second therapeutic agent. In some embodiments, the second therapeutic agent is an antiviral agent. In some embodiments, the second therapeutic agent is a viral vaccine. In some embodiments, the viral vaccine elicits an immune response in the subject against HIV (e.g., HIV-1 or HIV-2). In some embodiments, an Fc-domain-containing composition may be substituted for an Fc domain and an Fc-domain-monomer-containing composition may be substituted for an Fc domain monomer in any of the fusion proteins or conjugates described herein. In certain embodiments, the Fc-domain-containing composition is an antibody or an antibody fragment. An antibody may include any form of immunoglobulin, heavy chain antibody, light chain antibody, LRR-based antibody, or other protein scaffold with antibody-like properties, as well as any other immunological binding moiety known in the art, including antibody fragments (e.g., a Fd, Fv, Feb, scFv, or SMIP). The subunit structures and three-dimensional configurations of different classes of antibodies are known in the art. An antibody fragment may include a binding moiety that includes a portion derived from or having significant homology to an antibody, such as the antigen-determining region of an antibody. Exemplary antibody fragments include Fd, Fv, Feb, scFv, and SMIP. In particular embodiments, the antibody or antibody fragment is a human, mouse, camelid (e.g., llama, alpaca, or camel), goat, sheep, rabbit, chicken, guinea pig, hamster, horse, or rat antibody or antibody fragment. In specific embodiments, the antibody is an IgG, IgA, IgD, IgE, IgM, or intrabody. In certain embodiments, the antibody fragment includes an scFv, sdAb, dAb, Fd, Fv, Feb, or SMIP. In some embodiments, the Fc-domain-containing composition (e.g., an antibody or antibody fragment) confers binding specificity to a one or more targets (e.g., an antigen, such as an antigen associated with HIV). HIV-targeting antibodies are known in the art, for example, as described in Wibmer et al. Curr. Opin. HIV AIDS, 10(3): 135-143 (2015), which is incorporated herein by reference in its entirety. In some embodiments, the one or more targets (e.g., an antigen) bound by the Fc-domain- containing composition (e.g., an antibody or antibody fragment) is a viral (e.g., HIV) protein such as gp41 or gp120 receptor. In some embodiments, the antibody or antibody fragment recognizes a viral surface antigen. In some embodiments of any of the aspects described herein, the Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 1. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 1. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 2. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 2. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 3. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 3. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 4. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 4. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 5. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 5. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 6. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 6. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 7. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 7. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 8. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 8. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 9. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 9. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 10. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 10. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 11. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 11. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 12. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 12. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 13. In some embodiments, the Fc domain monome has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 13. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 14. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 14. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 15. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 15. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 16. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 16. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 17. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 17. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 18. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 19. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 19. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 20. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 21. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 21. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 22. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 22. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 23. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 23. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 24. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 24. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 25. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 25. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 26. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 26. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 27. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 27. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 28. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 28. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 29. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 29. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 30. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 30. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 31. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 31. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 32. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 32. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 33. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 33. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 34. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 34. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 35. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 35. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 36. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 36. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 37. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 37. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 38. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 38. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 39. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 39. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 40. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 40. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 41. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 41. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 42. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 42. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 43. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 43. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 44. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 45. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 46. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 46. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 47. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 47. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 48. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 48. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 49. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 49. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 50. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 50. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 51. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 51. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 52. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 52. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 53. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 53. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 54. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 54. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 55. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 55. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 56. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 56. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 57. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 57. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 58. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 58. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 59. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 59. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 60. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 60. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 61. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 61. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 62. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 62. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 63. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 63. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 64. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 64. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 65. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 65. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 66. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 66. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 67. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 67. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 68. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 68. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 69. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 69. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 70. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 70. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 71. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 71. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 72. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 72. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 73. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 73. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 74. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 74. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 75. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 75. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 76. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 76. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 77. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 77. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 133. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 133. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 134. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 134. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 135. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 135. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 136. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 136. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 137. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 137. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 138. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 138. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 139. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 139. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 140. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 140. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 141. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 141. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 142. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 142. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 143. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 143. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 144. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 144. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 145. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 145. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 146. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 146. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 147. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 147. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 148. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 148. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 149. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 149. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 150. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 150. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 151. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 151. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 152. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 152. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 153. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 153. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 154. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 154. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 155. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 155. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 156. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 156. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 157. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 157. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 158. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 158. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 159. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 159. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 160. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 160. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 161. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 161. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 162. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 162. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 163. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 163. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 164. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 164. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 165. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 165. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 166. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 166. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 167. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 167. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 168. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 168. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 169. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 169. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 170. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 171. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 171. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 172. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 173. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 173. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 174. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 174. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 175. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 175. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 176. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 176. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 177. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 177. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 178. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 178. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 179. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 179. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 180. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 180. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 181. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 181. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 182. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 182. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 183. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 183. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 184. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 184. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 185. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 185. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 186. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 186. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 187. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 187. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 188. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 188. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 189. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 189. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 190. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 190. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 191. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 191. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 192. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 192. In some embodiments of any of the aspects described herein, an Fc domain monomer (e.g., each Fc domain monomer) has or includes the amino acid sequence of SEQ ID NO: 193. In some embodiments, the Fc domain monomer has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 193. In some embodiments of any of the aspects described herein, the Fc domain monomer (e.g., the Fc domain monomer having the sequence of any one of SEQ ID NOs: 1-77 and 133-193) includes a triple mutation corresponding to M252Y/S254T/T256E (YTE). As used herein, an amino acid “corresponding to” a particular amino acid residue (e.g., of a particular SEQ ID NO.) should be understood to include any amino acid residue that one of skill in the art would understand to align to the particular residue (e.g., of the particular sequence). For example, any one of SEQ ID NOs: 1-77 and 133-193 may be mutated to include a YTE mutation. In some embodiments of any of the aspects described herein, the Fc domain monomer (e.g., the Fc domain monomer having the sequence of any one of SEQ ID NOs: 1-77 and 133-193) includes a double mutant corresponding to M428L/N434S (LS). As used herein, an amino acid “corresponding to” a particular amino acid residue (e.g., or a particular SEQ ID NO.) should be understood to include any amino acid residue that one of skill in the art would understand to align to the particular residue (e.g., of the particular sequence). For example, any one of SEQ ID NOs: 1-77 and 133-193 may be mutated to include a LS mutation. In some embodiments of any of the aspects described herein, the Fc domain monomer (e.g., the Fc domain monomer having the sequence of any one of SEQ ID NOs: 1-77 and 133-193) includes a mutant corresponding to N434H. As used herein, an amino acid “corresponding to” a particular amino acid residue (e.g., of a particular SEQ ID NO.) should be understood to include any amino acid residue that one of skill in the art would understand to align to the particular residue (e.g., of the particular sequence). For example, any one of SEQ ID NOs: 1-77 and 133-193 may be mutated to include an N434H mutation. In some embodiments of any of the aspects described herein, the Fc domain monomer (e.g., the Fc domain monomer having the sequence of any one of SEQ ID NOs: 1-77 and 133-193) includes a mutant corresponding to C220S. As used herein, an amino acid “corresponding to” a particular amino acid residue (e.g., or a particular SEQ ID NO.) should be understood to include any amino acid residue that one of skill in the art would understand to align to the particular residue (e.g., of the particular sequence). For example, any one of SEQ ID NOs: 1-77 and 133-193 may be mutated to include a C220S mutation. In some embodiments of any of the aspects described herein, the Fc domain monomer (e.g., the Fc domain monomer having the sequence of any one of SEQ ID NOs: 1-77 and 133-193) is a fragment of the Fc domain monomer (e.g., a fragment of at least 25 (e.g., 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), at least 50 (e.g., 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 or more), at least 75 (e.g., 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 or more) consecutive amino acids in length from SEQ ID NOs: 1-77 and 133-193. In some embodiments of any of the aspects described herein, a gp41-binding peptide (e.g., each gp41-binding peptide) has or includes the amino acid sequence of SEQ ID NO: 84. In some embodiments, the gp41-binding peptide has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 84. In some embodiments of any of the aspects described herein, a gp41-binding peptide (e.g., each gp41-binding peptide) has or includes the amino acid sequence of SEQ ID NO: 85. In some embodiments, the gp41-binding peptide has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 85. In some embodiments of any of the aspects described herein, a gp41-binding peptide (e.g., each gp41-binding peptide) has or includes the amino acid sequence of SEQ ID NO: 86. In some embodiments, the gp41-binding peptide has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 86. In some embodiments of any of the aspects described herein, a gp41-binding peptide (e.g., each gp41-binding peptide) has or includes the amino acid sequence of SEQ ID NO: 87. In some embodiments, the gp41-binding peptide has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 87. In some embodiments of any of the aspects described herein, a gp41-binding peptide (e.g., each gp41-binding peptide) has or includes the amino acid sequence of SEQ ID NO: 88. In some embodiments, the gp41-binding peptide has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 88. In some embodiments of any of the aspects described herein, a gp41-binding peptide (e.g., each gp41-binding peptide) has or includes the amino acid sequence of SEQ ID NO: 89. In some embodiments, the gp41-binding peptide has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 89. In some embodiments of any of the aspects described herein, a gp41-binding peptide (e.g., each gp41-binding peptide) has or includes the amino acid sequence of SEQ ID NO: 90. In some embodiments, the gp41-binding peptide has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 90. In some embodiments of any of the aspects described herein, a gp41-binding peptide (e.g., each gp41-binding peptide) has or includes the amino acid sequence of SEQ ID NO: 91. In some embodiments, the gp41-binding peptide has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 91. In some embodiments of any of the aspects described herein, a gp41-binding peptide (e.g., each gp41-binding peptide) has or includes the amino acid sequence of SEQ ID NO: 92. In some embodiments, the gp41-binding peptide has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 92. In some embodiments of any of the aspects described herein, a gp41-binding peptide (e.g., each gp41-binding peptide) has or includes the amino acid sequence of SEQ ID NO: 93. In some embodiments, the gp41-binding peptide has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 93. In some embodiments of any of the aspects described herein, a gp41-binding peptide (e.g., each gp41-binding peptide) has or includes the amino acid sequence of SEQ ID NO: 94. In some embodiments, the gp41-binding peptide has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 94. In some embodiments of any of the aspects described herein, the gp41-binding peptide (e.g., the gp41-binding peptide having the sequence of any one of SEQ ID NOs: 75-85) is a fragment of t the gp41- binding peptide (e.g., a fragment of at least 10 (e.g., at least 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) consecutive amino acids in length from SEQ ID NOs: 75-85. In some embodiments of any of the aspects described herein, the fusion protein comprises an amino acid sequence that shares at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity with an amino acid sequence selected from any one of SEQ ID NOs: 129-132 and 194-207. In some embodiments, the fusion protein comprises the amino acid of any one of SEQ ID NOs: 129-132 and 194- 207. In some embodiments of any one of SEQ ID NOs: 129-132 and 194-207, the C-terminal lysine residue is optionally present or absent. In some embodiments of any of the aspects described herein, the fusion protein (e.g., each fusion protein of a homodimer) has or includes the amino acid sequence of SEQ ID NO: 129. In some embodiments, the fusion protein has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 129. In some embodiments of any of the aspects described herein, the fusion protein (e.g., each fusion protein of a homodimer) has or includes the amino acid sequence of SEQ ID NO: 130. In some embodiments, the fusion protein has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 130. In some embodiments of any of the aspects described herein, the fusion protein (e.g., each fusion protein of a homodimer) has or includes the amino acid sequence of SEQ ID NO: 131. In some embodiments, the fusion protein has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 131. In some embodiments of any of the aspects described herein, the fusion protein (e.g., each fusion protein of a homodimer) has or includes the amino acid sequence of SEQ ID NO: 132. In some embodiments, the fusion protein has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 132. In some embodiments of any of the aspects described herein, the fusion protein (e.g., each fusion protein of a homodimer) has or includes the amino acid sequence of SEQ ID NO: 194. In some embodiments, the fusion protein has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 194. In some embodiments of any of the aspects described herein, the fusion protein (e.g., each fusion protein of a homodimer) has or includes the amino acid sequence of SEQ ID NO: 195. In some embodiments, the fusion protein has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 195. In some embodiments of any of the aspects described herein, the fusion protein (e.g., each fusion protein of a homodimer) has or includes the amino acid sequence of SEQ ID NO: 196. In some embodiments, the fusion protein has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 196. In some embodiments of any of the aspects described herein, the fusion protein (e.g., each fusion protein of a homodimer) has or includes the amino acid sequence of SEQ ID NO: 197. In some embodiments, the fusion protein has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 197. In some embodiments of any of the aspects described herein, the fusion protein (e.g., each fusion protein of a homodimer) has or includes the amino acid sequence of SEQ ID NO: 198. In some embodiments, the fusion protein has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 198. In some embodiments of any of the aspects described herein, the fusion protein (e.g., each fusion protein of a homodimer) has or includes the amino acid sequence of SEQ ID NO: 199. In some embodiments, the fusion protein has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 199. In some embodiments of any of the aspects described herein, the fusion protein (e.g., each fusion protein of a homodimer) has or includes the amino acid sequence of SEQ ID NO: 200. In some embodiments, the fusion protein has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 200. In some embodiments of any of the aspects described herein, the fusion protein (e.g., each fusion protein of a homodimer) has or includes the amino acid sequence of SEQ ID NO: 201. In some embodiments, the fusion protein has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 201. In some embodiments of any of the aspects described herein, the fusion protein (e.g., each fusion protein of a homodimer) has or includes the amino acid sequence of SEQ ID NO: 202. In some embodiments, the fusion protein has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 202. In some embodiments of any of the aspects described herein, the fusion protein (e.g., each fusion protein of a homodimer) has or includes the amino acid sequence of SEQ ID NO: 203. In some embodiments, the fusion protein has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 203. In some embodiments of any of the aspects described herein, the fusion protein (e.g., each fusion protein of a homodimer) has or includes the amino acid sequence of SEQ ID NO: 204. In some embodiments, the fusion protein has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 204. In some embodiments of any of the aspects described herein, the fusion protein (e.g., each fusion protein of a homodimer) has or includes the amino acid sequence of SEQ ID NO: 205. In some embodiments, the fusion protein has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 205. In some embodiments of any of the aspects described herein, the fusion protein (e.g., each fusion protein of a homodimer) has or includes the amino acid sequence of SEQ ID NO: 206. In some embodiments, the fusion protein has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 206. In some embodiments of any of the aspects described herein, the fusion protein (e.g., each fusion protein of a homodimer) has or includes the amino acid sequence of SEQ ID NO: 207. In some embodiments, the fusion protein has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 207. Definitions To facilitate the understanding of this invention, a number of terms are defined below. Terms defined herein have meanings as commonly understood by a person of ordinary skill in the areas relevant to the present invention. Terms such as "a", "an," and "the" are not intended to refer to only a singular entity, but include the general class of which a specific example may be used for illustration. The terminology herein is used to describe specific embodiments of the invention, but their usage does not delimit the invention, except as outlined in the claims. Any values provided in a range of values include both the upper and lower bounds, and any values contained within the upper and lower bounds. The term “about,” as used herein, indicates a deviation of ±5%. For example, about 10% refers to from 9.5% to 10.5%.drawing By “viral infection” is meant the pathogenic growth of a virus (e.g., the human immunodeficiency virus) in a host organism (e.g., a human subject). A viral infection can be any situation in which the presence of a viral population(s) is damaging to a host body. Thus, a subject is “suffering” from a viral infection when an excessive amount of a viral population is present in or on the subject’s body, or when the presence of a viral population(s) is damaging the cells or other tissue of the subject. As used herein, the term “Fc domain monomer” refers to a polypeptide chain that includes at least a hinge domain and second and third antibody constant domains (CH2 and CH3) or functional fragments thereof (e.g., fragments that that capable of (i) dimerizing with another Fc domain monomer to form an Fc domain, and (ii) binding to an Fc receptor. The Fc domain monomer can be any immunoglobulin antibody isotype, including IgG, IgE, IgM, IgA, or IgD (e.g., IgG). Additionally, the Fc domain monomer can be an IgG subtype (e.g., IgG1, IgG2a, IgG2b, IgG3, or IgG4) (e.g., IgG1). In some embodiments, an Fc domain monomer does not include any portion of an immunoglobulin that is capable of acting as an antigen-recognition region, e.g., a variable domain or a complementarity determining region (CDR). Fc domain monomers in the conjugates as described herein can contain one or more changes from a wild-type Fc domain monomer sequence (e.g., 1-10, 1-8, 1-6, 1-4 amino acid substitutions, additions, or deletions) that alter the interaction between an Fc domain and an Fc receptor. Examples of suitable changes are known in the art. In certain embodiments, a human Fc domain monomer (e.g., an IgG heavy chain, such as IgG1) includes a region that extends from any of Asn208, Glu216, Asp221, Lys222, or Cys226 to the carboxyl-terminus of the heavy chain at Lys447. C-terminal Lys447 of the Fc region may or may not be present, without affecting the structure or stability of the Fc region. Unless otherwise specified herein, numbering of amino acid residues in the IgG or Fc domain monomer is according to the EU numbering system for antibodies, also called the Kabat EU index, as described, for example, in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD, 1991. As used herein, the term “Fc domain” refers to a dimer of two Fc domain monomers that is capable of binding an Fc receptor. In the wild-type Fc domain, the two Fc domain monomers dimerize by the interaction between the two CH3 antibody constant domains, in some embodiments, one or more disulfide bonds form between the hinge domains of the two dimerizing Fc domain monomers. The term “covalently attached” refers to two parts of a conjugate that are linked to each other by a covalent bond formed between two atoms in the two parts of the conjugate. As used-herein, a “surface exposed amino acid” or “solvent-exposed amino acid,” such as a surface exposed cysteine or a surface exposed lysine refers to an amino acid that is accessible to the solvent surrounding the protein. A surface exposed amino acid may be a naturally-occurring or an engineered variant (e.g., a substitution or insertion) of the protein. In some embodiments, a surface exposed amino acid is an amino acid that when substituted does not substantially change the three- dimensional structure of the protein. The term “linker,” as used herein, refers to a covalent linkage or connection between two or more components in a fusion protein or a conjugate (e.g., between a gp41 binding peptide and an Fc domain monomer). In some embodiments, the linker is a bivalent linker, for example a linker connecting a gp41 binding peptide and an Fc domain monomer. Linkers may be chemical linkers, which are known to one of skill in the art, and are described in detail herein. Linkers may alternately be peptide linkers, such as those described herein. Molecules that may be used as linkers include at least two functional groups, which may be the same or different, e.g., two carboxylic acid groups, two amine groups, two sulfonic acid groups, a carboxylic acid group and a maleimide group, a carboxylic acid group and an alkyne group, a carboxylic acid group and an amine group, a carboxylic acid group and a sulfonic acid group, an amine group and a maleimide group, an amine group and an alkyne group, or an amine group and a sulfonic acid group. In a bivalent linker, the first functional group may form a covalent linkage with a first component and the second functional group may form a covalent linkage with the second component. Examples of dicarboxylic acids are described further herein. In some embodiments, a linker provides space, rigidity, and/or flexibility between the two or more components. In some embodiments, a linker may be a bond, e.g., a covalent bond. The term “bond” refers to a chemical bond, e.g., an amide bond, a disulfide bond, a C-O bond, a C-N bond, a N-N bond, a C-S bond, or any kind of bond created from a chemical reaction, e.g., chemical conjugation. In some embodiments, a linker includes no more than 250 atoms. In some embodiments, a linker includes no more than 250 non-hydrogen atoms. In some embodiments, the backbone of a linker includes no more than 250 atoms. The “backbone” of a linker refers to the atoms in the linker that together form the shortest path from one part of a conjugate to another part of the conjugate. The atoms in the backbone of the linker are directly involved in linking one part of a conjugate to another part of the conjugate. For examples, hydrogen atoms attached to carbons in the backbone of the linker are not considered as directly involved in linking one part of the conjugate to another part of the conjugate. In some embodiments, a linker may comprise a synthetic group derived from, e.g., a synthetic polymer (e.g., a polyethylene glycol (PEG) polymer). In some embodiments, a linker may comprise one or more amino acid residues, such as D- or L-amino acid residues. In some embodiments, a linker may be a residue of an amino acid sequence (e.g., a 1-25 amino acid, 1-10 amino acid, 1-9 amino acid, 1-8 amino acid, 1-7 amino acid, 1-6 amino acid, 1-5 amino acid, 1-4 amino acid, 1-3 amino acid, 1-2 amino acid, or 1 amino acid sequence). In some embodiments, a linker may comprise one or more, e.g., 1-100, 1-50, 1-25, 1-10, 1-5, or 1-3, optionally substituted alkylene, optionally substituted heteroalkylene (e.g., a PEG unit), optionally substituted alkenylene, optionally substituted heteroalkenylene, optionally substituted alkynylene, optionally substituted heteroalkynylene, optionally substituted cycloalkylene, optionally substituted heterocycloalkylene, optionally substituted cycloalkenylene, optionally substituted heterocycloalkenylene, optionally substituted cycloalkynylene, optionally substituted heterocycloalkynylene, optionally substituted arylene, optionally substituted heteroarylene (e.g., pyridine), O, S, NRⁱ (Rⁱ is H, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted alkenyl, optionally substituted heteroalkenyl, optionally substituted alkynyl, optionally substituted heteroalkynyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkenyl, optionally substituted cycloalkynyl, optionally substituted heterocycloalkynyl, optionally substituted aryl, or optionally substituted heteroaryl), P, carbonyl, thiocarbonyl, sulfonyl, phosphate, phosphoryl, or imino. For example, a linker may comprise one or more optionally substituted C₁-C₂₀ alkylene, optionally substituted C₁-C₂₀ heteroalkylene (e.g., a PEG unit), optionally substituted C₂-C₂₀ alkenylene (e.g., C2 alkenylene), optionally substituted C₂-C₂₀ heteroalkenylene, optionally substituted C₂-C₂₀ alkynylene, optionally substituted C₂-C₂₀ heteroalkynylene, optionally substituted C3-C20 cycloalkylene (e.g., cyclopropylene, cyclobutylene), optionally substituted C2-C20 heterocycloalkylene, optionally substituted C4-C20 cycloalkenylene, optionally substituted C4-C20 heterocycloalkenylene, optionally substituted C8-C20 cycloalkynylene, optionally substituted C8-C20 heterocycloalkynylene, optionally substituted C5-C15 arylene (e.g., C6 arylene), optionally substituted C3-C15 heteroarylene (e.g., imidazole, pyridine), O, S, NRⁱ (Rⁱ is H, optionally substituted C1-C20 alkyl, optionally substituted C1-C20 heteroalkyl, optionally substituted C2- C20 alkenyl, optionally substituted C₂-C₂₀ heteroalkenyl, optionally substituted C₂-C₂₀ alkynyl, optionally substituted C₂-C₂₀ heteroalkynyl, optionally substituted C3-C20 cycloalkyl, optionally substituted C2-C20 heterocycloalkyl, optionally substituted C4-C20 cycloalkenyl, optionally substituted C4-C20 heterocycloalkenyl, optionally substituted C8-C20 cycloalkynyl, optionally substituted C8-C20 heterocycloalkynyl, optionally substituted C5-C15 aryl, or optionally substituted C3-C15 heteroaryl), P, carbonyl, thiocarbonyl, sulfonyl, phosphate, phosphoryl, or imino. As used herein, the term “chemical linker” includes any linker described herein that does not include a polypeptide. For example, a chemical linker may include a hydrocarbon chain, which optionally includes one or more heteroatoms (e.g., an optionally substituted alkylene, heteroalkylene, alkenylene, heteroalkenylene, alkynylene, or heteroalkynylene). A chemical linker may include one or more cycloalkyl, heterocycloalkynyl, aryl, or heteroaryl rings within linker main chain. A chemical linker may include a polyethylene glycol (PEG) polymer, e.g., a PEG2-PEG50, most preferably PEG2, PEG3, PEG4, PEG5, PEG6, PEG7, PEG8, PEG9, or PEG10. A chemical linker may be a bond. As described in greater detail herein (see, e.g., conjugation chemistries), a chemical linker may include at least two functional groups, which may be the same or different, e.g., two carboxylic acid groups, two amine groups, two sulfonic acid groups, a carboxylic acid group and a maleimide group, a carboxylic acid group and an alkyne group, a carboxylic acid group and an amine group, a carboxylic acid group and a sulfonic acid group, an amine group and a maleimide group, an amine group and an alkyne group, or an amine group and a sulfonic acid group. In a bivalent linker, for example, the first functional group may form a covalent linkage with a first component and the second functional group may form a covalent linkage with the second component. As used interchangeably herein, the terms “peptide linker” or “polypeptide linker” includes any linker than comprises two or more amino acid residues. For example, a peptide linker may include 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 15 or more, 20 or more, 25 or more, 30 or more, 40 or more, or 50 or more amino acid residues, which are joined, for example by peptide bonds. The carboxy terminus of a peptide linker may be covalently conjugated (e.g., by a peptide bond) to a first moiety (e.g., an Fc domain monomer or a gp41-binding peptide) and the amino terminus of the peptide linker may be covalently conjugated (e.g., by a peptide bond) to a second moiety (e.g., an Fc domain monomer or a gp41 binding peptide), thereby conjugating the first moiety and the second moiety and allowing for space and/or flexibility between the first moiety and the second moiety. A peptide linker may be expressed from a polynucleotide construct or chemically synthesized and subsequently chemically conjugated to a first moiety and a second moiety. Alternately, a peptide linker may be expressed in tandem with a first polypeptide (e.g., an Fc domain monomer or a gp41-binding peptide) and a second polypeptide (e.g., an Fc domain monomer or a gp41-binding peptide), thereby joining the first polypeptide and the second polypeptide to form a fusion protein. The terms “alkyl,” “alkenyl,” and “alkynyl,” as used herein, include straight-chain and branched- chain monovalent substituents, as well as combinations of these, containing only C and H when unsubstituted. When the alkyl group includes at least one carbon-carbon double bond or carbon-carbon triple bond, the alkyl group can be referred to as an “alkenyl” or “alkynyl” group respectively. The monovalency of an alkyl, alkenyl, or alkynyl group does not include the optional substituents on the alkyl, alkenyl, or alkynyl group. For example, if an alkyl, alkenyl, or alkynyl group is attached to a compound, monovalency of the alkyl, alkenyl, or alkynyl group refers to its attachment to the compound and does not include any additional substituents that may be present on the alkyl, alkenyl, or alkynyl group. In some embodiments, the alkyl or heteroalkyl group may contain, e.g., 1-20.1-18, 1-16, 1-14, 1-12, 1-10, 1-8, 1- 6, 1-4, or 1-2 carbon atoms (e.g., C1-C20, C1-C18, C1-C16, C1-C14, C1-C12, C1-C10, C1-C8, C1-C6, C1-C4, or C1-C2). In some embodiments, the alkenyl, heteroalkenyl, alkynyl, or heteroalkynyl group may contain, e.g., 2-20, 2-18, 2-16, 2-14, 2-12, 2-10, 2-8, 2-6, or 2-4 carbon atoms (e.g., C₂-C₂₀, C2-C18, C2-C16, C2-C14, C2-C12, C2-C10, C2-C8, C2-C6, or C2-C4). Examples include, but are not limited to, methyl, ethyl, isobutyl, sec-butyl, tert-butyl, 2-propenyl, and 3-butynyl. The term “cycloalkyl,” as used herein, represents a monovalent saturated or unsaturated non- aromatic cyclic alkyl group. A cycloalkyl may have, e.g., three to twenty carbons (e.g., a C3-C7, C3-C8, C3-C9, C3-C10, C3-C11, C3-C12, C3-C14, C3-C16, C3-C18, or C3-C20 cycloalkyl). Examples of cycloalkyls include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl. When the cycloalkyl group includes at least one carbon-carbon double bond, the cycloalkyl group can be referred to as a “cycloalkenyl” group. A cycloalkenyl may have, e.g., four to twenty carbons (e.g., a C4- C7, C4-C8, C4-C9, C4-C10, C4-C11, C4-C12, C4-C14, C4-C16, C4-C18, or C4-C20 cycloalkenyl). Exemplary cycloalkenyl groups include, but are not limited to, cyclopentenyl, cyclohexenyl, and cycloheptenyl. When the cycloalkyl group includes at least one carbon-carbon triple bond, the cycloalkyl group can be referred to as a “cycloalkynyl” group. A cycloalkynyl may have, e.g., eight to twenty carbons (e.g., a C8-C9, C8-C10, C8-C11, C8-C12, C8-C14, C8-C16, C8-C18, or C8-C20 cycloalkynyl). The term “cycloalkyl” also includes a cyclic compound having a bridged multicyclic structure in which one or more carbons bridges two non-adjacent members of a monocyclic ring, e.g., bicyclo[2.2.1.]heptyl and adamantane. The term “cycloalkyl” also includes bicyclic, tricyclic, and tetracyclic fused ring structures, e.g., decalin and spiro cyclic compounds. A “heterocycloalkyl,” “heterocycloalkenyl,” or “heterocycloalkynyl” group refers to a cycloalkyl, cycloalkenyl, or cycloalkynyl group having one or more rings (e.g., 1, 2, 3, 4 or more rings) that has one or more heteroatoms independently selected from, e.g., N, O, and S. Exemplary heterocycloalkyl groups include pyrrolidine, thiophene, thiolane, tetrahydrofuran, piperidine, tetrahydropyran, quinoline, isoquinoline, cinnoline, pthalazine, quinazoline, quinoxaline, indole, benzothiophene, benzofuran, isoindole, benzo[c]thiophene, isobenzofuran, benzimidaole, benzoxazole, benzothiazole, 1H-indazole, 1,2,benzisoxazole, 1,2-benzisothiazole, 2,1-benzisothiazole, 2,1- benzisoxazole, purine, pyrrolizidine, indene, fluorene, carbazole, dibenzofuran, acridine, phenazine, and phenoxazine. The term “aryl,” as used herein, refers to any monocyclic or fused ring bicyclic or tricyclic system which has the characteristics of aromaticity in terms of electron distribution throughout the ring system, e.g., phenyl, naphthyl, or phenanthrene. In some embodiments, a ring system contains 5-15 ring member atoms or 5-10 ring member atoms. An aryl group may have, e.g., five to fifteen carbons (e.g., a C5-C6, C5-C7, C5-C8, C5-C9, C5-C10, C5-C11, C5-C12, C5-C13, C5-C14, or C5-C15 aryl). The term “heteroaryl” also refers to such monocyclic or fused bicyclic ring systems containing one or more, e.g., 1- 4, 1-3, 1, 2, 3, or 4, heteroatoms selected from O, S and N. A heteroaryl group may have, e.g., two to fifteen ring member atoms (e.g., a C2-C3, C2-C4, C2-C5, C2-C6, C2-C7, C2-C8, C2-C9. C2-C10, C2- C11, C2-C12, C2-C13, C2-C14, or C3-C15 heteroaryl). The inclusion of a heteroatom permits inclusion of 5-membered rings to be considered aromatic as well as 6-membered rings. Thus, typical heteroaryl systems include, e.g., pyridyl, pyrimidyl, indolyl, benzimidazolyl, benzotriazolyl, isoquinolyl, quinolyl, benzothiazolyl, benzofuranyl, thienyl, furyl, pyrrolyl, thiazolyl, triazolyl (e.g., 1,2,3- or 1,2,4-triazolyl) oxazolyl, isoxazolyl, benzoxazolyl, benzoisoxazolyl, and imidazolyl. Because tautomers are possible, a group such as phthalimido is also considered heteroaryl. In some embodiments, the aryl or heteroaryl group is a 5- or 6-membered aromatic rings system optionally containing 1-2 nitrogen atoms. In some embodiments, the aryl or heteroaryl group is an optionally substituted phenyl, pyridyl, indolyl, pyrimidyl, pyridazinyl, benzothiazolyl, benzimidazolyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, or imidazopyridinyl. In some embodiments, the aryl group is phenyl. In some embodiments, an aryl group may be optionally substituted with a substituent such an aryl substituent, e.g., biphenyl. The term “alkaryl,” refers to an aryl group that is connected to an alkylene, alkenylene, or alkynylene group. In general, if a compound is attached to an alkaryl group, the alkylene, alkenylene, or alkynylene portion of the alkaryl is attached to the compound. In some embodiments, an alkaryl is C6- C35 alkaryl (e.g., C6-C16, C6-C14, C6-C12, C6-C10, C6-C9, C6-C8, C7, or C6 alkaryl), in which the number of carbons indicates the total number of carbons in both the aryl portion and the alkylene, alkenylene, or alkynylene portion of the alkaryl. Examples of alkaryls include, but are not limited to, (C1- C8)alkylene(C6-C12)aryl, (C2-C8)alkenylene(C6-C12)aryl, or (C2-C8)alkynylene(C6-C12)aryl. In some embodiments, an alkaryl is benzyl or phenethyl. In a heteroalkaryl, one or more heteroatoms selected from N, O, and S may be present in the alkylene, alkenylene, or alkynylene portion of the alkaryl group and/or may be present in the aryl portion of the alkaryl group. In an optionally substituted alkaryl, the substituent may be present on the alkylene, alkenylene, or alkynylene portion of the alkaryl group and/or may be present on the aryl portion of the alkaryl group. The term “amino,” as used herein, represents –N(R^x)2 or –N⁺(R^x)3, where each R^x is, independently, H, alkyl, alkenyl, alkynyl, aryl, alkaryl, cycloalkyl, or two R^x combine to form a heterocycloalkyl. In some embodiment, the amino group is -NH2. The term “alkamino,” as used herein, refers to an amino group, described herein, that is attached to an alkylene (e.g., C1-C5 alkylene), alkenylene (e.g., C2-C5 alkenylene), or alkynylene group (e.g., C2- C5 alkenylene). In general, if a compound is attached to an alkamino group, the alkylene, alkenylene, or alkynylene portion of the alkamino is attached to the compound. The amino portion of an alkamino refers to –N(R^x)2 or –N⁺(R^x)3, where each R^x is, independently, H, alkyl, alkenyl, alkynyl, aryl, alkaryl, cycloalkyl, or two R^x combine to form a heterocycloalkyl. In some embodiment, the amino portion of an alkamino is -NH2. An example of an alkamino group is C1-C5 alkamino, e.g., C2 alkamino (e.g., CH2CH2NH2 or CH2CH2N(CH3)2). In a heteroalkamino group, one or more, e.g., 1-4, 1-3, 1, 2, 3, or 4, heteroatoms selected from N, O, and S may be present in the alkylene, alkenylene, or alkynylene portion of the heteroalkamino group. In some embodiments, an alkamino group may be optionally substituted. In a substituted alkamino group, the substituent may be present on the alkylene, alkenylene, or alkynylene portion of the alkamino group and/or may be present on the amino portion of the alkamino group. The term “alkamide,” as used herein, refers to an amide group that is attached to an alkylene (e.g., C1-C5 alkylene), alkenylene (e.g., C2-C5 alkenylene), or alkynylene (e.g., C2-C5 alkenylene) group. In general, if a compound is attached to an alkamide group, the alkylene, alkenylene, or alkynylene portion of the alkamide is attached to the compound. The amide portion of an alkamide refers to –C(O)-N(R^x)2, where each R^x is, independently, H, alkyl, alkenyl, alkynyl, aryl, alkaryl, cycloalkyl, or two R^x combine to form a heterocycloalkyl. In some embodiment, the amide portion of an alkamide is -C(O)NH2. An alkamide group may be -(CH2)2-C(O)NH2 or -CH2-C(O)NH2. In a heteroalkamide group, one or more, e.g., 1-4, 1-3, 1, 2, 3, or 4, heteroatoms selected from N, O, and S may be present in the alkylene, alkenylene, or alkynylene portion of the heteroalkamide group. In some embodiments, an alkamide group may be optionally substituted. In a substituted alkamide group, the substituent may be present on the alkylene, alkenylene, or alkynylene portion of the alkamide group and/or may be present on the amide portion of the alkamide group. The terms “alkylene,” “alkenylene,” and “alkynylene,” as used herein, refer to divalent groups having a specified size. In some embodiments, an alkylene may contain, e.g., 1-20, 1-18, 1-16, 1-14, 1- 12, 1-10, 1-8, 1-6, 1-4, or 1-2 carbon atoms (e.g., C1-C20, C1-C18, C1-C16, C1-C14, C1-C12, C1-C10, C1-C8, C1-C6, C1-C4, or C1-C2). In some embodiments, an alkenylene or alkynylene may contain, e.g., 2-20, 2-18, 2-16, 2-14, 2-12, 2-10, 2-8, 2-6, or 2-4 carbon atoms (e.g., C₂-C₂₀, C2-C18, C2-C16, C2- C14, C2-C12, C2-C10, C2-C8, C2-C6, or C2-C4). Alkylene, alkenylene, and/or alkynylene includes straight-chain and branched-chain forms, as well as combinations of these. Alkylene, alkenylene, and/or alkynylene groups can be substituted by the groups typically suitable as substituents for alkyl, alkenyl and alkynyl groups as set forth herein. For example, C=O is a C1 alkylene that is substituted by an oxo (=O). For example, -HCR-C≡C- may be considered as an optionally substituted alkynylene and is considered a divalent group even though it has an optional substituent, R. Heteroalkylene, heteroalkenylene, and/or heteroalkynylene groups refer to alkylene, alkenylene, and/or alkynylene groups including one or more, e.g., 1-4, 1-3, 1, 2, 3, or 4, heteroatoms, e.g., N, O, and S. For example, a polyethylene glycol (PEG) polymer or a PEG unit -(CH2)2-O- in a PEG polymer is considered a heteroalkylene containing one or more oxygen atoms. The term “cycloalkylene,” as used herein, refers to a divalent cyclic group linking together two parts of a compound. For example, one carbon within the cycloalkylene group may be linked to one part of the compound, while another carbon within the cycloalkylene group may be linked to another part of the compound. A cycloalkylene group may include saturated or unsaturated non-aromatic cyclic groups. A cycloalkylene may have, e.g., three to twenty carbons in the cyclic portion of the cycloalkylene (e.g., a C3-C7, C3-C8, C3-C9, C3-C10, C3-C11, C3-C12, C3-C14, C3-C16, C3-C18, or C3-C20 cycloalkylene). When the cycloalkylene group includes at least one carbon-carbon double bond, the cycloalkylene group can be referred to as a “cycloalkenylene” group. A cycloalkenylene may have, e.g., four to twenty carbons in the cyclic portion of the cycloalkenylene (e.g., a C4-C7, C4-C8, C4-C9. C4-C10, C4-C11, C4- C12, C4-C14, C4-C16, C4-C18, or C4-C20 cycloalkenylene). When the cycloalkylene group includes at least one carbon-carbon triple bond, the cycloalkylene group can be referred to as a “cycloalkynylene” group. A cycloalkynylene may have, e.g., four to twenty carbons in the cyclic portion of the cycloalkynylene (e.g., a C4-C7, C4-C8, C4-C9. C4-C10, C4-C11, C4-C12, C4-C14, C4-C16, C4-C18, or C8-C20 cycloalkynylene). A cycloalkylene group can be substituted by the groups typically suitable as substituents for alkyl, alkenyl and alkynyl groups as set forth herein. Heterocycloalkylene refers to a cycloalkylene group including one or more, e.g., 1-4, 1-3, 1, 2, 3, or 4, heteroatoms, e.g., N, O, and S. Examples of cycloalkylenes include, but are not limited to, cyclopropylene and cyclobutylene. A tetrahydrofuran may be considered as a heterocycloalkylene. The term “arylene,” as used herein, refers to a multivalent (e.g., divalent or trivalent) aryl group linking together multiple (e.g., two or three) parts of a compound. For example, one carbon within the arylene group may be linked to one part of the compound, while another carbon within the arylene group may be linked to another part of the compound. An arylene may have, e.g., five to fifteen carbons in the aryl portion of the arylene (e.g., a C5-C6, C5-C7, C5-C8, C5-C9. C5-C10, C5-C11, C5-C12, C5-C13, C5- C14, or C5-C15 arylene). An arylene group can be substituted by the groups typically suitable as substituents for alkyl, alkenyl and alkynyl groups as set forth herein. Heteroarylene refers to an aromatic group including one or more, e.g., 1-4, 1-3, 1, 2, 3, or 4, heteroatoms, e.g., N, O, and S. A heteroarylene group may have, e.g., two to fifteen carbons (e.g., a C2-C3, C2-C4, C2-C5, C2-C6, C2-C7, C2-C8, C2- C9. C2-C10, C2-C11, C2-C12, C2-C13, C2-C14, or C3-C15 heteroarylene). The term “optionally substituted,” as used herein, refers to having 0, 1, or more substituents, such as 0-25, 0-20, 0-10 or 0-5 substituents. Substituents include, but are not limited to, alkyl, alkenyl, alkynyl, aryl, alkaryl, acyl, heteroaryl, heteroalkyl, heteroalkenyl, heteroalkynyl, heteroalkaryl, halogen, oxo, cyano, nitro, amino, alkamino, hydroxy, alkoxy, alkanoyl, carbonyl, carbamoyl, guanidinyl, ureido, amidinyl, any of the groups or moieties described above, and hetero versions of any of the groups or moieties described above. Substituents include, but are not limited to, F, Cl, methyl, phenyl, benzyl, OR, NR2, SR, SOR, SO2R, OCOR, NRCOR, NRCONR2, NRCOOR, OCONR2, RCO, COOR, alkyl-OOCR, SO3R, CONR2, SO2NR2, NRSO2NR2, CN, CF3, OCF3, SiR3, and NO2, wherein each R is, independently, H, alkyl, alkenyl, aryl, heteroalkyl, heteroalkenyl, or heteroaryl, and wherein two of the optional substituents on the same or adjacent atoms can be joined to form a fused, optionally substituted aromatic or nonaromatic, saturated or unsaturated ring which contains 3–8 members, or two of the optional substituents on the same atom can be joined to form an optionally substituted aromatic or nonaromatic, saturated or unsaturated ring which contains 3–8 members. An optionally substituted group or moiety refers to a group or moiety (e.g., any one of the groups or moieties described above) in which one of the atoms (e.g., a hydrogen atom) is optionally replaced with another substituent. For example, an optionally substituted alkyl may be an optionally substituted methyl, in which a hydrogen atom of the methyl group is replaced by, e.g., OH. As another example, a substituent on a heteroalkyl or its divalent counterpart, heteroalkylene, may replace a hydrogen on a carbon or a hydrogen on a heteroatom such as N. For example, the hydrogen atom in the group -R-NH-R- may be substituted with an alkamide substituent, e.g., -R-N[(CH2C(O)N(CH3)2]-R. The term “hetero,” when used to describe a chemical group or moiety, refers to having at least one heteroatom that is not a carbon or a hydrogen, e.g., N, O, and S. Any one of the groups or moieties described above may be referred to as hetero if it contains at least one heteroatom. For example, a heterocycloalkyl, heterocycloalkenyl, or heterocycloalkynyl group refers to a cycloalkyl, cycloalkenyl, or cycloalkynyl group that has one or more heteroatoms independently selected from, e.g., N, O, and S. An example of a heterocycloalkenyl group is a maleimido. For example, a heteroaryl group refers to an aromatic group that has one or more heteroatoms independently selected from, e.g., N, O, and S. One or more heteroatoms may also be included in a substituent that replaced a hydrogen atom in a group or moiety as described herein. For example, in an optionally substituted heteroaryl group, if one of the hydrogen atoms in the heteroaryl group is replaced with a substituent (e.g., methyl), the substituent may also contain one or more heteroatoms (e.g., methanol). T^{he term “acyl,” as used herein,}

^{, wherein Rz is} an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, alkaryl, alkamino, heteroalkyl, heteroalkenyl, heteroalkynyl, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, heteroaryl, heteroalkaryl, or heteroalkamino. The term “halo” or “halogen,” as used herein, refers to any halogen atom, e.g., F, Cl, Br, or I. Any one of the groups or moieties described herein may be referred to as a “halo moiety” if it contains at least one halogen atom, such as haloalkyl. The term “hydroxyl,” as used herein, represents an -OH group. The term “oxo,” as used herein, refers to a substituent having the structure =O, where there is a double bond between an atom and an oxygen atom. The term “carbonyl,” as used herein, refers to a group having the structure:

. The term “thiocarbonyl,” as used herein, refers to a group having the structure: The term “phosphate,” as used herein, represents the group having the structu

re: .

The term “phosphoryl,” as used herein, represents the group having the structure:

or

. The term “sulfonyl,” as used herein, represents the group having the structure:

The term “imino,” as used herein, represents the group having the structure:

wherein R is an optional substituent. The term “N-protecting group,” as used herein, represents those groups intended to protect an ^{amino group against undesirable reactions during synthetic procedures. Commonly used N-protecting} groups are disclosed in Greene, “Protective Groups in Organic Synthesis,” 5th Edition (John Wiley & Sons, New York, 2014), which is incorporated herein by reference. N-protecting groups include, e.g., acyl, aryloyl, and carbamyl groups such as formyl, acetyl, propionyl, pivaloyl, t-butylacetyl, 2-chloroacetyl, 2-bromoacetyl, trifluoroacetyl, trichloroacetyl, phthalyl, o-nitrophenoxyacetyl, α-chlorobutyryl, benzoyl, carboxybenzyl (CBz), 4-chlorobenzoyl, 4-bromobenzoyl, 4-nitrobenzoyl, and chiral auxiliaries such as protected or unprotected D, L or D, L-amino acid residues such as alanine, leucine, phenylalanine; sulfonyl-containing groups such as benzenesulfonyl and p-toluenesulfonyl; carbamate forming groups such as benzyloxycarbonyl, p-chlorobenzyloxycarbonyl, p-methoxybenzyloxycarbonyl, p- nitrobenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl, p-bromobenzyloxycarbonyl, 3,4- dimethoxybenzyloxycarbonyl, 3,5-dimethoxybenzyl oxycarbonyl, 2,4-dimethoxybenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 2-nitro-4,5-dimethoxybenzyloxycarbonyl, 3,4,5-trimethoxybenzyloxycarbonyl, 1-(p-biphenylyl)-1-methylethoxycarbonyl, α,α-dimethyl- 3,5-dimethoxybenzyloxycarbonyl, benzhydryloxy carbonyl, t-butyloxycarbonyl (BOC), diisopropylmethoxycarbonyl, isopropyloxycarbonyl, ethoxycarbonyl, methoxycarbonyl, allyloxycarbonyl, 2,2,2,-trichloroethoxycarbonyl, phenoxycarbonyl, 4-nitrophenoxy carbonyl, fluorenyl-9-methoxycarbonyl (Fmoc), cyclopentyloxycarbonyl, adamantyloxycarbonyl, cyclohexyloxycarbonyl, and phenylthiocarbonyl; alkaryl groups such as benzyl, triphenylmethyl, and benzyloxymethyl; and silyl groups such as trimethylsilyl. As used interchangeably herein, the terms “protein,” “peptide,” and “polypeptide” refer to ^{compounds comprising amino acids joined by way of a peptide bonds.} The term “amino acid,” as used herein, means naturally occurring amino acids and non-naturally occurring amino acids. As used herein, the term “fusion protein” refers to any conjugate which includes two or more peptides, polypeptides, or proteins, which are covalently linked. The two or more peptides, polypeptides, or proteins may be covalently conjugated by a linker, e.g., any of the linkers described herein, including a chemical linker, a peptide linker, or a bond. For example, a fusion protein may include one or more gp41- binding peptides and one or more Fc domain monomers. The one or more gp41-binding peptides and one or more Fc domain monomers may be encoded by the same polynuceotide sequence (e.g., a single continuous polynucleotide sequence that is operably linked) and expressed as a single polypeptide construct. Alternately, the one or more gp41-binding peptide and the one or more Fc domain monomers may be encoded by separate polynucleotides (e.g., polynucleotide sequences that are not continuous, and can be either on the same vector or separate vectors), expressed as separate polypeptide constructs, and subsequently covalently conjugated by any of the linkers and/or conjugation chemistries described herein. The term “naturally occurring amino acids,” as used herein, means amino acids including Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, and Val. The term “non-naturally occurring amino acid,” as used herein, means an alpha amino acid that is not naturally produced or found in a mammal. Examples of non-naturally occurring amino acids include D-amino acids; an amino acid having an acetylaminomethyl group attached to a sulfur atom of a cysteine; a pegylated amino acid; the omega amino acids of the formula NH2(CH2)nCOOH where n is 2-6, neutral nonpolar amino acids, such as sarcosine, t-butyl alanine, t-butyl glycine, N-methyl isoleucine, and norleucine; oxymethionine; phenylglycine; citrulline; methionine sulfoxide; cysteic acid; ornithine; diaminobutyric acid; 3-aminoalanine; 3-hydroxy-D-proline; 2,4-diaminobutyric acid; 2-aminopentanoic acid; 2-aminooctanoic acid, 2-carboxy piperazine; piperazine-2-carboxylic acid, 2-amino-4-phenylbutanoic acid; 3-(2-naphthyl)alanine, and hydroxyproline. Other amino acids are α-aminobutyric acid, α-amino-α- methylbutyrate, aminocyclopropane-carboxylate, aminoisobutyric acid, aminonorbornyl-carboxylate, L- cyclohexylalanine, cyclopentylalanine, L-N-methylleucine, L-N-methylmethionine, L-N-methylnorvaline, L- N-methylphenylalanine, L-N-methylproline, L-N-methylserine, L-N-methyltryptophan, D-ornithine, L-N- methylethylglycine, L-norleucine, α-methyl-aminoisobutyrate, α-methylcyclohexylalanine, D-α- methylalanine, D-α-methylarginine, D-α-methylasparagine, D-α-methylaspartate, D-α-methylcysteine, D- α-methylglutamine, D-α-methylhistidine, D-α-methylisoleucine, D-α-methylleucine, D-α-methyllysine, D-α- methylmethionine, D-α-methylornithine, D-α-methylphenylalanine, D-α-methylproline, D-α-methylserine, D-N-methylserine, D-α-methylthreonine, D-α-methyltryptophan, D-α-methyltyrosine, D-α-methylvaline, D- N-methylalanine, D-N-methylarginine, D-N-methylasparagine, D-N-methylaspartate, D-N-methylcysteine, D-N-methylglutamine, D-N-methylglutamate, D-N-methylhistidine, D-N-methylisoleucine, D-N- methylleucine, D-N-methyllysine, N-methylcyclohexylalanine, D-N-methylornithine, N-methylglycine, N- methylaminoisobutyrate, N-(1-methylpropyl)glycine, N-(2-methylpropyl)glycine, D-N-methyltryptophan, D- N-methyltyrosine, D-N-methylvaline, γ-aminobutyric acid, L-t-butylglycine, L-ethylglycine, L- homophenylalanine, L-α-methylarginine, L-α-methylaspartate, L-α-methylcysteine, L-α-methylglutamine, L-α-methylhistidine, L-α-methylisoleucine, L-α-methylleucine, L-α-methylmethionine, L-α-methylnorvaline, L-α-methylphenylalanine, L-α-methylserine, L-α-methyltryptophan, L-α-methylvaline, N-(N-(2,2- diphenylethyl) carbamylmethylglycine, 1-carboxy-1-(2,2-diphenyl-ethylamino) cyclopropane, 4- hydroxyproline, ornithine, 2-aminobenzoyl (anthraniloyl), D-cyclohexylalanine, 4-phenyl-phenylalanine, L- citrulline, α-cyclohexylglycine, L-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, L-thiazolidine-4- carboxylic acid, L-homotyrosine, L-2-furylalanine, L-histidine (3-methyl), N-(3-guanidinopropyl)glycine, O- methyl-L-tyrosine, O-glycan-serine, meta-tyrosine, nor-tyrosine, L-N,N′,N″-trimethyllysine, homolysine, norlysine, N-glycan asparagine, 7-hydroxy-1,2,3,4-tetrahydro-4-fluorophenylalanine, 4- methylphenylalanine, bis-(2-picolyl)amine, pentafluorophenylalanine, indoline-2-carboxylic acid, 2- aminobenzoic acid, 3-amino-2-naphthoic acid, asymmetric dimethylarginine, L-tetrahydroisoquinoline-1- carboxylic acid, D-tetrahydroisoquinoline-1-carboxylic acid, 1-amino-cyclohexane acetic acid, D/L- allylglycine, 4-aminobenzoic acid, 1-amino-cyclobutane carboxylic acid, 2 or 3 or 4-aminocyclohexane carboxylic acid, 1-amino-1-cyclopentane carboxylic acid, 1-aminoindane-1-carboxylic acid, 4-amino- pyrrolidine-2-carboxylic acid, 2-aminotetraline-2-carboxylic acid, azetidine-3-carboxylic acid, 4-benzyl- pyrolidine-2-carboxylic acid, tert-butylglycine, b-(benzothiazolyl-2-yl)-alanine, b-cyclopropyl alanine, 5,5- dimethyl-1,3-thiazolidine-4-carboxylic acid, (2R,4S)4-hydroxypiperidine-2-carboxylic acid, (2S,4S) and (2S,4R)-4-(2-naphthylmethoxy)-pyrolidine-2-carboxylic acid, (2S,4S) and (2S,4R)4-phenoxy-pyrrolidine-2- carboxylic acid, (2R,5S)and(2S,5R)-5-phenyl-pyrrolidine-2-carboxylic acid, (2S,4S)-4-amino-1-benzoyl- pyrrolidine-2-carboxylic acid, t-butylalanine, (2S,5R)-5-phenyl-pyrrolidine-2-carboxylic acid, 1- aminomethyl-cyclohexane-acetic acid, 3,5-bis-(2-amino)ethoxy-benzoic acid, 3,5-diamino-benzoic acid, 2- methylamino-benzoic acid, N-methylanthranylic acid, L-N-methylalanine, L-N-methylarginine, L-N- methylasparagine, L-N-methylaspartic acid, L-N-methylcysteine, L-N-methylglutamine, L-N- methylglutamic acid, L-N-methylhistidine, L-N-methylisoleucine, L-N-methyllysine, L-N-methylnorleucine, L-N-methylornithine, L-N-methylthreonine, L-N-methyltyrosine, L-N-methylvaline, L-N-methyl-t- butylglycine, L-norvaline, α-methyl-γ-aminobutyrate, 4,4′-biphenylalanine, α-methylcylcopentylalanine, α- methyl-α-napthylalanine, α-methylpenicillamine, N-(4-aminobutyl)glycine, N-(2-aminoethyl)glycine, N-(3- aminopropyl)glycine, N-amino-α-methylbutyrate, α-napthylalanine, N-benzylglycine, N-(2- carbamylethyl)glycine, N-(carbamylmethyl)glycine, N-(2-carboxyethyl)glycine, N-(carboxymethyl)glycine, N-cyclobutylglycine, N-cyclodecylglycine, N-cycloheptylglycine, N-cyclohexylglycine, N-cyclodecylglycine, N-cylcododecylglycine, N-cyclooctylglycine, N-cyclopropylglycine, N-cycloundecylglycine, N-(2,2- diphenylethyl)glycine, N-(3,3-diphenylpropyl)glycine, N-(3-guanidinopropyl)glycine, N-(1- hydroxyethyl)glycine, N-(hydroxyethyl))glycine, N-(imidazolylethyl))glycine, N-(3-indolylyethyl)glycine, N- methyl-γ-aminobutyrate, D-N-methylmethionine, N-methylcyclopentylalanine, D-N-methylphenylalanine, D-N-methylproline, D-N-methylthreonine, N-(1-methylethyl)glycine, N-methyl-napthylalanine, N- methylpenicillamine, N-(p-hydroxyphenyl)glycine, N-(thiomethyl)glycine, penicillamine, L-α-methylalanine, L-α-methylasparagine, L-α-methyl-t-butylglycine, L-methylethylglycine, L-α-methylglutamate, L-α- methylhomophenylalanine, N-(2-methylthioethyl)glycine, L-α-methyllysine, L-α-methylnorleucine, L-α- methylornithine, L-α-methylproline, L-α-methylthreonine, L-α-methyltyrosine, L-N-methyl- homophenylalanine, N-(N-(3,3-diphenylpropyl) carbamylmethylglycine, L-pyroglutamic acid, D- pyroglutamic acid, O-methyl-L-serine, O-methyl-L-homoserine, 5-hydroxylysine, α-carboxyglutamate, phenylglycine, L-pipecolic acid (homoproline), L-homoleucine, L-lysine (dimethyl), L-2-naphthylalanine, L- dimethyldopa or L-dimethoxy-phenylalanine, L-3-pyridylalanine, L-histidine (benzoyloxymethyl), N- cycloheptylglycine, L-diphenylalanine, O-methyl-L-homotyrosine, L-β-homolysine, O-glycan-threoine, Ortho-tyrosine, L-N,N′-dimethyllysine, L-homoarginine, neotryptophan, 3-benzothienylalanine, isoquinoline-3-carboxylic acid, diaminopropionic acid, homocysteine, 3,4-dimethoxyphenylalanine, 4- chlorophenylalanine, L-1,2,3,4-tetrahydronorharman-3-carboxylic acid, adamantylalanine, symmetrical dimethylarginine, 3-carboxythiomorpholine, D-1,2,3,4-tetrahydronorharman-3-carboxylic acid, 3- aminobenzoic acid, 3-amino-1-carboxymethyl-pyridin-2-one, 1-amino-1-cyclohexane carboxylic acid, 2- aminocyclopentane carboxylic acid, 1-amino-1-cyclopropane carboxylic acid, 2-aminoindane-2-carboxylic acid, 4-amino-tetrahydrothiopyran-4-carboxylic acid, azetidine-2-carboxylic acid, b-(benzothiazol-2-yl)- alanine, neopentylglycine, 2-carboxymethyl piperidine, b-cyclobutyl alanine, allylglycine, diaminopropionic acid, homo-cyclohexyl alanine, (2S,4R)- 4-hydroxypiperidine-2-carboxylic acid, octahydroindole-2- carboxylic acid, (2S,4R) and (2S,4R)-4-(2-naphthyl), pyrrolidine-2-carboxylic acid, nipecotic acid, (2S,4R)and (2S,4S)-4-(4-phenylbenzyl) pyrrolidine-2-carboxylic acid, (3S)-1-pyrrolidine-3-carboxylic acid, (2S,4S)-4-tritylmercapto-pyrrolidine-2-carboxylic acid, (2S,4S)-4-mercaptoproline, t-butylglycine, N,N- bis(3-aminopropyl)glycine, 1-amino-cyclohexane-1-carboxylic acid, N-mercaptoethylglycine, and selenocysteine. In some embodiments, amino acid residues may be charged or polar. Charged amino acids include alanine, lysine, aspartic acid, or glutamic acid, or non-naturally occurring analogs thereof. Polar amino acids include glutamine, asparagine, histidine, serine, threonine, tyrosine, methionine, or tryptophan, or non-naturally occurring analogs thereof. It is specifically contemplated that in some embodiments, a terminal amino group in the amino acid may be an amido group or a carbamate group. As used herein, the term “percent (%) identity” refers to the percentage of amino acid residues of a candidate sequence, e.g., an Fc-IgG, or fragment thereof, that are identical to the amino acid residues of a reference sequence after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent identity (i.e., gaps can be introduced in one or both of the candidate and reference sequences for optimal alignment and non-homologous sequences can be disregarded for comparison purposes). Alignment for purposes of determining percent identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, ALIGN, or Megalign (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared. In some embodiments, the percent amino acid sequence identity of a given candidate sequence to, with, or against a given reference sequence (which can alternatively be phrased as a given candidate sequence that has or includes a certain percent amino acid sequence identity to, with, or against a given reference sequence) is calculated as follows: 100 x (fraction of A/B) where A is the number of amino acid residues scored as identical in the alignment of the candidate sequence and the reference sequence, and where B is the total number of amino acid residues in the reference sequence. In some embodiments where the length of the candidate sequence does not equal to the length of the reference sequence, the percent amino acid sequence identity of the candidate sequence to the reference sequence would not equal to the percent amino acid sequence identity of the reference sequence to the candidate sequence. Two polynucleotide or polypeptide sequences are said to be “identical” if the sequence of nucleotides or amino acids in the two sequences is the same when aligned for maximum correspondence as described above. Comparisons between two sequences are typically performed by comparing the sequences over a comparison window to identify and compare local regions of sequence similarity. A “comparison window” as used herein, refers to a segment of at least about 15 contiguous positions, about 20 contiguous positions, about 25 contiguous positions, or more (e.g., about 30 to about 75 contiguous positions, or about 40 to about 50 contiguous positions), in which a sequence may be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned. The term “treating” or “to treat,” as used herein, refers to a therapeutic treatment of a viral infection (e.g., a viral infection such as an HIV infection) in a subject. In some embodiments, a therapeutic treatment may slow the progression of the viral infection, improve the subject’s outcome, and/or eliminate the infection. In some embodiments, a therapeutic treatment of a viral infection in a subject may eliminate or ameliorate of one or more symptoms or conditions associated with the viral infection, diminish the extent of the viral, stabilize (i.e., not worsening) the state of the viral infection, prevent the spread of the viral infection, and/or delay or slow the progress of the viral infection, as compare the state and/or the condition of the viral infection in the absence of the therapeutic treatment. The term “subject,” as used herein, can be a human or non-human primate, or other mammal, such as but not limited to dog, cat, horse, cow, pig, turkey, goat, fish, monkey, chicken, rat, mouse, or sheep. The term “therapeutically effective amount,” as used herein, refers to an amount, e.g., pharmaceutical dose, effective in inducing a desired effect in a subject or in treating a subject having a condition or disorder described herein (e.g., a viral infection, such as an HIV infection). It is also to be understood herein that a “therapeutically effective amount” may be interpreted as an amount giving a desired therapeutic and/or preventative effect, taken in one or more doses or in any dosage or route, and/or taken alone or in combination with other therapeutic agents (e.g., an antiviral agent described herein). For example, in the context of administering a fusion protein or a conjugate described herein that is used for the treatment of a viral infection, an effective amount of the fusion protein or conjugate is, for example, an amount sufficient to prevent, slow down, or reverse the progression of the viral infection as compared to the response obtained without administration of the fusion protein or the conjugate. As used herein, the term “pharmaceutical composition” refers to a medicinal or pharmaceutical formulation that contains at least one active ingredient (e.g., a fusion protein or a conjugate described herein) as well as one or more excipients and diluents to enable the active ingredient suitable for the method of administration. The pharmaceutical composition of the present disclosure includes pharmaceutically acceptable components that are compatible with a conjugate described herein (e.g., a fusion protein or a conjugate described herein). As used herein, the term “pharmaceutically acceptable carrier” refers to an excipient or diluent in a pharmaceutical composition. For example, a pharmaceutically acceptable carrier may be a vehicle capable of suspending or dissolving the active ingredients (e.g., a fusion protein or a conjugate). The pharmaceutically acceptable carrier must be compatible with the other ingredients of the formulation and not deleterious to the recipient. In the present disclosure, the pharmaceutically acceptable carrier must provide adequate pharmaceutical stability to a fusion protein or a conjugate described herein. The nature of the carrier differs with the mode of administration. For example, for oral administration, a solid carrier is preferred; for intravenous administration, an aqueous solution carrier (e.g., WFI, and/or a buffered solution) is generally used. The term “pharmaceutically acceptable salt,” as used herein, represents a salt of a fusion protein or conjugate described herein that are, within the scope of sound medical judgment, suitable for use in methods described herein without undue toxicity, irritation, and/or allergic response. Pharmaceutically acceptable salts are well known in the art. For example, pharmaceutically acceptable salts are described in: Pharmaceutical Salts: Properties, Selection, and Use (Eds. P.H. Stahl and C.G. Wermuth), Wiley- VCH, 2008. The salts can be prepared in situ during the final isolation and purification of the conjugates described herein or separately by reacting the free base group with a suitable organic acid. The term “gp41-binding peptide,” as used herein, refers to a peptide (e.g., a peptide having from 5-100 amino acids) that binds to the HIV gp41 glycoprotein. By binding to the gp41 glycoprotein of the virus, the gp41-binding peptide prevents the creation of an entry pore for the capsid of the virus, thereby inhibiting the entry of the HIV virus into the cell. Gp41-binding peptide include, but are not limited to, peptides having at least 85% sequence identity, including sequences having 100% sequence identity with, the amino acid sequence of any one of SEQ ID NOs: 84-94. SEQ ID NO.84, for example, corresponds to the amino acid sequence of enfuvirtide (Fuseon^TM, Roche) which is an FDA approved antiretroviral therapy. Other features and advantages of the conjugates described herein will be apparent from the following Detailed Description and the claims. Description of the Drawings FIG.1 is a set of images depicting exemplary fusion proteins including at least one gp41-binding peptide and at least one fc domain monomers, where the Fc domain monomer of the fusion protein is homodimerized to form an Fc domain. FIG.2 is a graph showing plasma levels of a conjugate including an Fc domain having a C220S mutation (SEQ ID NO: 64) (2 mpk IV) compared to a conjugate including an Fc domain having a C220S mutation and a YTE triple mutation (SEQ ID NO: 67) (2 mpk IV) in non-human primate PK studies determined by Fc capture. This study was performed as described in Example 1. FIG.3 shows an image of a non-reducing (NR) and reducing (R) SDS-PAGE of fusion proteins having the amino acid sequences of SEQ ID NOs: 129 and 130. FIG.4 shows an image of a non-reducing (NR) and reducing (R) SDS-PAGE of fusion proteins having the amino acid sequences of SEQ ID NOs: 131 and 132. Detailed Description This disclosure relates to fusion proteins, conjugates, compositions, methods for inhibiting viral growth, and methods for the treatment of viral infections. In particular, the invention features fusion proteins which include at least one peptide that binds to HIV glycoprotein 41 (gp41) and at least one Fc domain monomer. The Fc domain monomer of each of two fusions proteins may dimerize to form an Fc domain, where each monomer of the Fc domain is conjugated to at least on gp41-binding peptide. HIV binds to the host CD4 cell receptor via the viral protein gp120. Upon binding to gp 120, viral transmembrane protein gp140 undergoes a conformational change that assists in the fusion of the viral membrane to the host cell membrane. Accordingly, the gp41-binding peptide of the fusion proteins described herein prevents viral attachment fusion and entry into the host immune cell. The Fc monomers or Fc domains in the conjugates bind to FcγRs (e.g., FcRn, FcγRI, FcγRIIa, FcγRIIc, FcγRIIIa, and FcγRIIIb) on immune cells, e.g., neutrophils, to activate phagocytosis and effector functions, such as antibody-dependent cell-mediated cytotoxicity (ADCC), thus leading to the engulfment and destruction of viral particles by immune cells and further enhancing the antiviral activity. Such compositions are useful in methods for the inhibition of viral growth and in methods for the treatment of viral infections, such as those caused by an HIV-1 and HIV-2. I. Viral Infections The fusion proteins, conjugates, and pharmaceutical compositions described herein are used to treat a viral infection (e.g., an HIV-1 or HIV-2 viral infection). Viral infection refers to the pathogenic growth of a virus (e.g., the human immunodeficiency virus) in a host organism (e.g., a human subject). A viral infection can be any situation in which the presence of a viral population(s) is damaging to a host body. Thus, a subject is suffering from a viral infection when an excessive amount of a viral population is present in or on the subject’s body, or when the presence of a viral population(s) is damaging the cells or other tissue of the subject. The human immunodeficiency viruses (HIV) are two species of Lentivirus (a subgroup of retrovirus) that causes HIV infection and over time acquired immunodeficiency syndrome (AIDS). AIDS is a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Without treatment, average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype. In most cases, HIV is a sexually transmitted infection and occurs by contact with or transfer of blood, pre-ejaculate, semen, and vaginal fluids. Two types of HIV have been characterized: HIV-1 and HIV-2. HIV infects vital cells in the human immune system, such as helper T cells (specifically CD4+ T cells), macrophages, and dendritic cells. HIV infection leads to low levels of CD4+ T cells through a number of mechanisms, including pyroptosis of abortively infected T cells, apoptosis of uninfected bystander cells, direct viral killing of infected cells, and killing of infected CD4+ T cells by CD8+ cytotoxic lymphocytes that recognize infected cells. When CD4+ T cell numbers decline below a critical level, cell-mediated immunity is lost, and the body becomes progressively more susceptible to opportunistic infections, leading to the development of AIDS. II. Fusion proteins The invention features fusion proteins which include at least one Fc domain monomer conjugated to at least one (e.g., one or two) gp41-binding peptides (FIG.1). An exemplary fusion protein of the invention includes the structure: (P₂-L₂)n₂-B-(L₁-P₁)n₁, wherein B is an Fc domain monomer (e.g., and Fc domain monomer including the amino acid sequence of any one of SEQ ID NOs: 1-77 and 133-193); P₁ and P₂ are each independently a gp41-binding peptide (e.g., a gp41-binding peptide including the amino acid sequence of any one of SEQ ID NOs: 75-85); L₁ and L₂ are each independently a linker (e.g., a chemical linker or a peptide linker); and n₁ and n₂ are each independently 0 or 1, wherein at least one of n₁ and n₂ is 1 (e.g., the fusion protein must include at least on gp41-binding peptide). In some embodiments, the fusion protein includes one Fc domain monomer conjugated to one gp41-binding peptide. For example, n₁ is 1, n₂ is 0, and the fusion protein comprises the structure: B-L₁- P₁. The Fc domain and the gp41-binding peptide may be conjugated in any orientation. Where a C-to-N conjugation occurs, the Fc domain and the gp41-peptide may be expressed as a single polypeptide construct including a polypeptide linker or may be expressed separately and subsequently conjugated via a polypeptide or chemical linker. Where an C-to-C or N-to-N conjugation occurs, the Fc domain and the gp41-binding peptide are expressed separately and subsequently conjugated, e.g., via a chemical or peptide linker. For example, the linker (L₁) may be conjugated to C-terminus of the Fc domain monomer (B) and to the N-terminus of the gp41-binding peptide (P₁). Alternately, the linker (L₁) may be conjugated to N-terminus of the Fc domain monomer (B) and to the C-terminus of the gp41-binding peptide (P₁). Alternately, the linker (L₁) is conjugated to N-terminus of the Fc domain monomer (B) and to the N- terminus of the gp41-binding peptide (P₁). Alternately, the linker (L₁) is conjugated to C-terminus of the Fc domain monomer (B) and to the C-terminus of the gp41-binding peptide (P₁). In some embodiments, the fusion protein includes one Fc domain monomer conjugated to one gp41-binding peptide. For example, n₁ is 1, n₂ is 1, and the fusion protein comprises the structure: P₂-L₂- B-L₁-P₁. As described above, conjugation can occur in any orientation, and the fusion protein may be expressed as a singly polypeptide construct, or may be assembled by chemical conjugation. For example, the linker (L₂) may be conjugated to the C-terminus of the gp41-binding peptide (P₂) and to the N-terminus of the Fc domain monomer (B), and the linker (L₁) may be conjugated to the C-terminus of the Fc domain monomer (B) and to the N-terminus of the gp41-binding peptide (P₁). Alternately, the linker (L₂) may be conjugated to the N-terminus of the gp41-binding peptide (P₂) and to the N-terminus of the Fc domain monomer (B), and the linker (L₁) may be conjugated to the N-terminus of the gp41-binding peptide (P₁) and to the C-terminus of the Fc domain monomer (B). Alternately, the linker (L₂) may be conjugated to the C-terminus of the gp41-binding peptide (P₂) and to the N-terminus of the Fc domain monomer (B), and the linker (L₁) may be conjugated to the C-terminus of the gp41-binding peptide (P₁) and to the C-terminus of the Fc domain monomer (B). In some embodiments, the fusion protein is a fusion protein of Table 1. In some embodiments, the fusion protein is a fusion protein of Table 1, wherein the linker (L₁) is a chemical linker or a peptide linker. In preferred embodiments of Table 1, L₁ is a peptide linker, such as a peptide linker having 2-100 amino acid residues, such as any peptide linker described herein. In some embodiments, the peptide linker has the formula (G4S)x, where x is an integer from 1 to 10. In some embodiments, the fusion protein is a fusion protein of Table 2. In some embodiments, the fusion protein includes an amino acid sequence that shares at least 85% sequence identity (e.g., at least 90%, 95%, 98%, or 99% sequence identity) with an amino acid sequence selected from any one of the fusion proteins of Table 2. In some embodiments, the fusion protein (e.g., a fusion protein of Table 1 or 2) includes an Fc domain having at least 85% sequence identity (e.g., at least 90%, 95%, 98%, or 99% sequence identity) with the amino acid sequence of any one of SEQ ID NO: 63, SEQ ID NO: 64. SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO:76, or SEQ ID NO: 77. In some embodiments, the fusion protein (e.g., a fusion protein of Table 1 or 2) includes a Gp41 binding peptide having at least 85% sequence identity (e.g., at least 90%, 95%, 98%, or 99% sequence identity) with the amino acid sequence of any one of SEQ ID NO: 90, SEQ ID NO: 91, or SEQ ID NO: 94. In some embodiments, the fusion protein has or includes the amino acid sequence of any one of SEQ ID NOs: 129-132 and 194-207. In some embodiments, the fusion protein has or includes an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of any one of SEQ ID NOs: 129-132 and 194-207. The C-terminal lysine residue of any one of SEQ ID NOs: 129-132 and 194-207 may be present or absent (e.g., without affecting the structure or function of the fusion protein). The C-terminal lysine residue may be proteolytically cleaved following expression of the fusion protein (e.g., in a cell).

The disclosure also provides a conjugate including a first fusion protein selected from any of the gp41 binding peptide-Fc domain monomer fusion proteins described herein; and a second fusion protein selected from any of the gp41 binding peptide-Fc domain monomer fusion proteins described herein; wherein the Fc domain monomer (B) of the first fusion protein and the Fc domain monomer (B) of the second fusion protein dimerize to form an Fc domain. In some embodiments, the first fusion protein and the second fusion protein have the same structure and the conjugate is a homodimer. III. Fc domain monomers and Fc domains The disclosure provides fusion proteins and conjugates which include one or more Fc domain monomers. When two fusions protein including an Fc domain monomer dimerize, the resulting conjugate includes an Fc domain. An Fc domain monomer includes a hinge domain, a CH2 antibody constant domain, and a CH3 antibody constant domain. The Fc domain monomer can be of immunoglobulin antibody isotype IgG, IgE, IgM, IgA, or IgD. The Fc domain monomer can also be of any immunoglobulin antibody isotype (e.g., IgG1, IgG2a, IgG2b, IgG3, or IgG4). The Fc domain monomer can be of any immunoglobulin antibody allotype (e.g., IGHG1*01 (i.e., G1m(za)), IGHG1*07 (i.e., G1m(zax)), IGHG1*04 (i.e., G1m(zav)), IGHG1*03 (G1m(f)), IGHG1*08 (i.e., G1m(fa)), IGHG2*01, IGHG2*06, IGHG2*02, IGHG3*01, IGHG3*05, IGHG3*10, IGHG3*04, IGHG3*09, IGHG3*11, IGHG3*12, IGHG3*06, IGHG3*07, IGHG3*08, IGHG3*13, IGHG3*03, IGHG3*14, IGHG3*15, IGHG3*16, IGHG3*17, IGHG3*18, IGHG3*19, IGHG2*04, IGHG4*01, IGHG4*03, or IGHG4*02) (as described in, for example, in Vidarsson et al. IgG subclasses and allotypes: from structure to effector function. Frontiers in Immunology.5(520):1-17 (2014)). The Fc domain monomer can also be of any species, e.g., human, murine, or mouse. A dimer of Fc domain monomers is an Fc domain that can bind to an Fc receptor, which is a receptor located on the surface of leukocytes. In some embodiments, an Fc domain monomer described herein may contain one or more amino acid substitutions, additions, and/or deletion relative to an Fc domain monomer having a sequence of any one of SEQ ID NOs: 1-77 and 133-193. In some embodiments, an Asn in an Fc domain monomer in the conjugates as described herein may be replaced by Ala in order to prevent N-linked glycosylation (see, e.g., SEQ ID NOs: 12-15, where Asn to Ala substitution is labeled with *). In some embodiments, an Fc domain monomer in the conjugates described herein may also containing additional Cys additions (see, e.g., SEQ ID NOs: 9, 10, and 11, where Cys additions are labeled with *). In some embodiments, an Fc domain monomer in the fusion proteins or conjugates as described herein includes an additional moiety for purification (e.g., a hexa-histidine peptide (HHHHHH (SEQ ID NO: 78)), or a signal sequence (e.g., IL₂ signal sequence MYRMQLLSCIALSLALVTNS (SEQ ID NO: 79)) attached to the N- or C-terminus of the Fc domain monomer. In some embodiments, an Fc domain monomer in the conjugate does not contain any type of antibody variable region, e.g., VH, VL, a complementarity determining region (CDR), or a hypervariable region (HVR). In some embodiments, an Fc domain monomer in the fusion proteins or conjugates as described herein may have a sequence that is at least 95% identical (e.g., 97%, 99%, or 99.5% identical) to the sequence of any one of SEQ ID NOs: 1-77 and 133-193 shown below. In some embodiments, an Fc domain monomer in the fusion proteins or conjugates as described herein may have a sequence of any one of SEQ ID NOs: 1-77 and 133-193 shown below.

SEQ ID NO: 26: mature human IgG1 Fc with Human Serum Albumin Signal Sequence (bold) at the N- terminus, N-terminal ISAMVRS amino acid residues added (underlined), with H310A (*) and H435A (*) mutations to impede FcRn binding, C-terminal G4S (italicized), and C-terminal C-myc tag (underlined, italicized)

SEQ ID NO: 30: mature human IgG1 Fc with N-terminal MVRS amino acid residues added (underlined), Asn to Ala substitution (*), C-terminal G4S linker (italicized), and C-terminal mutated (lysine to phenylalanine bold) C-myc tag (underlined italicized)

SEQ ID NO: 35: human IgG1 Fc with murine IgG signal sequence (bold) at the N-terminus, with removal of EPKSSD hinge residues from the N-terminus of the mature human IgG1 Fc, allotype G1m(fa) (bold italics)

As defined herein, an Fc domain includes two Fc domain monomers that are dimerized by the interaction between the CH3 antibody constant domains, as well as one or more disulfide bonds that form between the hinge domains of the two dimerizing Fc domain monomers. An Fc domain forms the minimum structure that binds to an Fc receptor, e.g., Fc-gamma receptors (i.e., Fcγ receptors (FcγR)), Fc-alpha receptors (i.e., Fcα receptors (FcαR)), Fc-epsilon receptors (i.e., Fcε receptors (FcεR)), and/or the neonatal Fc receptor (FcRn). In some embodiments, an Fc domain of the present invention binds to an Fcγ receptor (e.g., FcRn, FcγRI (CD64), FcγRIIa (CD32), FcγRIIb (CD32), FcγRIIIa (CD16a), FcγRIIIb (CD16b)), and/or FcγRIV and/or the neonatal Fc receptor (FcRn). In some embodiments, the Fc domain monomer or Fc domain of the invention is an aglycosylated Fc domain monomer or Fc domain (e.g., an Fc domain monomer or an Fc domain that maintains engagement to an Fc receptor (e.g., FcRn). For example, the Fc domain is an aglycosylated IgG1 variants that maintains engagement to an Fc receptor (e.g., an IgG1 having an amino acid substitution at N297 and/or T299 of the glycosylation motif). Exemplary aglycosylated Fc domains and methods for making aglycosylated Fc domains are known in the art, for example, as described in Sazinsky S.L. et al., Aglycosylated immunoglobulin G1 variants productively engage activating Fc receptors, PNAS, 2008, 105(51):20167-20172, which is incorporated herein in its entirety. In some embodiments, the Fc domain or Fc domain monomer of the invention is engineered to enhance binding to the neonatal Fc receptor (FcRn). For example, the Fc domain may include the triple mutation corresponding to M252Y/S254T/T256E (YTE) (e.g., an IgG1, such as a human or humanized IgG1 having a YTE mutation, for example SEQ ID NO: 33, SEQ ID NO: 36, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 56, or SEQ ID NO: 57). The Fc domain may include the double mutant corresponding to M428L/N434S (LS) (e.g., an IgG1, such as a human or humanized IgG1 having an LS mutation, such as SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 59). The Fc domain may include the single mutant corresponding to N434H (e.g., an IgG1, such as a human or humanized IgG1 having an N434H mutation). The Fc domain may include the single mutant corresponding to C220S (e.g., and IgG1, such as a human or humanized IgG1 having a C220S mutation, such as SEQ ID NO: 34, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, or SEQ ID NO:77). The Fc domain may include a combination of one or more of the above-described mutations that enhance binding to the FcRn. Enhanced binding to the FcRn may increase the half-life Fc domain-containing conjugate. For example, incorporation of one or more amino acid mutations that increase binding to the FcRn (e.g., a YTE mutation, an LS mutation, or an N434H mutation) may increase the half-life of the conjugate by 5%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%.100%, 200%, 300%, 400%, 500% or more relative to a conjugate having an the corresponding Fc domain without the mutation that enhances FcRn binding. Exemplary Fc domains with enhanced binding to the FcRN and methods for making Fc domains having enhanced binding to the FcRN are known in the art, for example, as described in Maeda, A. et al., Identification of human IgG1 variant with enhanced FcRn binding and without increased binding to rheumatoid factor autoantibody, MABS, 2017, 9(5):844-853, which is incorporated herein in its entirety. As used herein, an amino acid “corresponding to” a particular amino acid residue (e.g., of a particular SEQ ID NO.) should be understood to include any amino acid residue that one of skill in the art would understand to align to the particular residue (e.g., of the particular sequence). For example, any one of SEQ ID NOs: 1-77 and 133-193 may be mutated to include a YTE mutation, an LS mutation, and/or an N434H mutation by mutating the “corresponding residues” of the amino acid sequence. As used herein, a sulfur atom “corresponding to” a particular cysteine residue of a particular SEQ ID NO. should be understood to include the sulfur atom of any cysteine residue that one of skill in the art would understand to align to the particular cysteine of the particular sequence. The protein sequence alignment of human IgG1 (UniProtKB: P01857; SEQ ID NO: 80), human IgG2 (UniProtKB: P01859; SEQ ID NO: 81), human IgG3 (UniProtKB: P01860; SEQ ID NO: 82), and human IgG4 (UniProtKB: P01861; SEQ ID NO: 83) is provided below (aligned with Clustal Omega Multiple Pairwise Alignment). The alignment indicates cysteine residues (e.g., sulfur atoms of cysteine residues) that “correspond to” one another (in boxes and indicated by the • symbol). One of skill in the art would readily be able to perform such an alignment with any IgG variant of the invention to determine the sulfur atom of a cysteine that corresponds to any sulfur atom of a particular cysteine of a particular SEQ ID NO. described herein (e.g., any one of SEQ ID NOs: 1-77 and 133-193). For example, one of skill in the art would readily be able to determine that Cys10 of SEQ ID NO: 10 (the first cysteine of the conserved CPPC motif of the hinge region of the Fc domain) corresponds to, for example, Cys109 of IgG1, Cys106 of IgG2, Cys156 of IgG3, Cys29 of SEQ ID NO: 1, Cys9 of SEQ ID NO: 2, Cys30 of SEQ ID NO: 3, or Cys10 of SEQ ID NO: 10. In some embodiments, the Fc domain or Fc domain monomer of the invention has the sequence of any one of SEQ ID NOs: 1-77 and 133-193 may further include additional amino acids at the N- terminus (Xaa)x and/or additional amino acids at the C-terminus (Xaa)z, wherein Xaa is any amino acid and x and z are a whole number greater than or equal to zero, generally less than 100, prefereably less than 10 and more preferably 0, 1, 2, 3, 4, or 5. For example, the additional amino acids may be a single amino acid on the C-terminus corresponding to Lys330 of IgG1. As used herein, a nitrogen atom “corresponding to” a particular lysine residue of a particular SEQ ID NO. should be understood to include the nitrogen atom of any lysine residue that one of skill in the art would understand to align to the particular lysine of the particular sequence. The protein sequence alignment of human IgG1 (UniProtKB: P01857; SEQ ID NO: 80), human IgG2 (UniProtKB: P01859; SEQ ID NO: 81), human IgG3 (UniProtKB: P01860; SEQ ID NO: 82), and human IgG4 (UniProtKB: P01861; SEQ ID NO: 83) is provided below (aligned with Clustal Omega Multiple Pairwise Alignment). The alignment indicates lysine residues (e.g., nitrogen atoms of lysine residues) that “correspond to” one another (in boxes and indicated by the * symbol). One of skill in the art would readily be able to perform such an alignment with any IgG variant of the invention to determine the nitrogen atom of a lysine that corresponds to any nitrogen atom of a particular lysine of a particular SEQ ID NO. described herein (e.g., any one of SEQ ID NOs: 1-77 and 133-193). For example, one of skill in the art would readily be able to determine that Lys35 of SEQ ID NO: 10 corresponds to, for example, Lys129 of IgG1, Lys126 of IgG2, Lys176 of IgG3, Lys51 of SEQ ID NO: 1, Lys31 of SEQ ID NO: 2, Lys50 of SEQ ID NO: 3, or Lys30 of SEQ ID NO: 10.

Protein sequence alignment of lgG1 (SEQ ID NO: 80), lgG2 (SEQ ID NO: 81), lgG3 (SEQ ID NO: 82), and lgG4 (SEQ ID NO: 83)

Activation of Immune Cells

Fc-gamma receptors (FcyFts) bind the Fc portion of immunoglobulin G (IgG) and play important roles in immune activation and regulation. For example, the IgG Fc domains in immune complexes (ICs) engage FcyFts with high avidity, thus triggering signaling cascades that regulate immune cell activation. The human FcyFt family contains several activating receptors (FcyFtl, FcyFtlla, FcyFtllc, FcyFtllla, and FcγRIIIb) and one inhibitory receptor (FcγRIIb). FcγR signaling is mediated by intracellular domains that contain immune tyrosine activating motifs (ITAMs) for activating FcγRs and immune tyrosine inhibitory motifs (ITIM) for inhibitory receptor FcγRIIb. In some embodiments, FcγR binding by Fc domains results in ITAM phosphorylation by Src family kinases; this activates Syk family kinases and induces downstream signaling networks, which include PI3K and Ras pathways. In the fusion proteins or conjugates described herein, the Fc domain portion of the fusion protein or conjugate bind to FcγRs (e.g., FcRn, FcγRI, FcγRIIa, FcγRIIc, FcγRIIIa, and FcγRIIIb) on immune cells and activate phagocytosis and effector functions, such as antibody-dependent cell-mediated cytotoxicity (ADCC), thus leading to the engulfment and destruction of viral particles by immune cells and further enhancing the antiviral activity of the conjugates. Examples of immune cells that may be activated by the conjugates described herein include, but are not limited to, macrophages, neutrophils, eosinophils, basophils, lymphocytes, follicular dendritic cells, natural killer cells, and mast cells. IV. Glycoprotein 41-binding peptides The disclosure provides fusion proteins and conjugates which include one or more glycoprotein 41 (gp41)-binding peptides. Gp41-binding peptides bind to the HIV gp41. By binding to gp41 of the virus, the gp41-binding peptide prevents the creation of an entry pore for the capsid of the virus, thereby inhibiting the entry of the HIV virus into the cell. Gp41-binding peptides include any peptide, e.g., a peptide having a length of 5-100, 5-50, 5-30, 5-20, 10-100, 10-50, 10-30, or 10-20 amino acids, which binds specifically to HIV gp41 (e.g., binds to gp41 with at least 2-fold, 5-fold, 10-fold, 50-fold, 100-fold, 500-fold, or 1000-fold greater affinity that to another protein, e.g., another HIV protein). Gp41-binding peptides include, but are not limited to, peptides having at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of any one of SEQ ID NOs: 75-85. Gp41-binding peptides having the amino acid sequence of any one of SEQ ID NOs: 75-85 are known to inhibit viral replication (see, e.g., Pu et al. Development of Protein- and Peptide-Based HIV Entry Inhibitors Targeting gp120 or gp41. Viruses.11, 705 (2019), which is incorporated herein by reference in its entirety). SEQ ID NO.84 corresponds to the amino acid sequence of enfuvirtide (FuseonTM, Roche) which is an FDA approved antiretroviral therapy. SEQ ID NO: 82 corresponds to the amino acid sequence of 2P₂3, an artificial antiretroviral peptide, that has been shown to exhibit potent antiviral activity against HIV-1, HIV-2, and SIV (see, e.g., Xiong et al. A helical short- peptide fusion inhibitor with highly potent activity against human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus. J Virol.91:e01839-16. doi.org/10.1128/JVI.01839-16 (2017), which is incorporated herein by reference in its entirety). SEQ ID NO: 94 corresponds to the amino acid sequence of AP3, another non-native protein sequence which has been shown to exhibit potent antiviral activity (see, e.g., Zhu et al. Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy. Scientific Reports.5, 13028; doi: 10.1038/srep13028 (2015), which is incorporated herein by reference in its entirety). A gp41-binding peptide of the disclosure may be a fragment of a gp41-binding peptide described herein, (e.g., a fragment of at least 10 (e.g., at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) consecutive amino acids in length from SEQ ID NOs: 84-94. A gp41-binding peptide retains the ability to bind specifically to HIV gp41.

V. Linkers A linker refers to a linkage or connection between two or more components in a fusion protein or a conjugate described herein (e.g., between a gp41 binding peptide and an Fc domain monomer). A linker can be a simple covalent bond, e.g., a peptide bond, a synthetic polymer, e.g., a polyethylene glycol (PEG) polymer, or any kind of bond created from a chemical reaction, e.g. chemical conjugation. In the case that a linker is a peptide bond, the carboxylic acid group at the C-terminus of one protein domain can react with the amino group at the N-terminus of another protein domain in a condensation reaction to form a peptide bond. Specifically, the peptide bond can be formed from synthetic means through a conventional organic chemistry reaction well-known in the art, or by natural production from a host cell, wherein a polynucleotide sequence encoding the DNA sequences of both proteins, e.g., two Fc domain monomer, in tandem series can be directly transcribed and translated into a contiguous polypeptide encoding both proteins by the necessary molecular machineries, e.g., DNA polymerase and ribosome, in the host cell. In the case that a linker is a synthetic polymer, e.g., a PEG polymer, the polymer can be functionalized with reactive chemical functional groups at each end to react with the terminal amino acids at the connecting ends of two proteins. In the case that a linker (except peptide bond mentioned above) is made from a chemical reaction, chemical functional groups, e.g., amine, carboxylic acid, ester, azide, or other functional groups commonly used in the art, can be attached synthetically to the C-terminus of one protein and the N- terminus of another protein, respectively. The two functional groups can then react to through synthetic chemistry means to form a chemical bond, thus connecting the two proteins together. Such chemical conjugation procedures are routine for those skilled in the art. Peptide linkers In the present invention, a linker between a gp41-binding peptide and an Fc domain monomer (e.g. L₁ or L₂) can be polypeptide including 3-200 amino acids (e.g., 3-200, 3-180, 3-160, 3-140, 3-120, 3- 100, 3-90, 3-80, 3-70, 3-60, 3-50, 3-45, 3-40, 3-35, 3-30, 3-25, 3-20, 3-15, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3- 4, 4-200, 5-200, 6-200, 7-200, 8-200, 9-200, 10-200, 15-200, 20-200, 25-200, 30-200, 35-200, 40-200, 45-200, 50-200, 60-200, 70-200, 80-200, 90-200, 100-200, 120-200, 140-200, 160-200, or 180-200 amino acids). In some embodiments, a linker between a gp41-binding peptide and an Fc domain monomer (e.g. L₁ or L₂) is an polypeptide containing at least 12 amino acids, such as 12-200 amino acids (e.g., 12-200, 12-180, 12-160, 12-140, 12-120, 12-100, 12-90, 12-80, 12-70, 12-60, 12-50, 12-40, 12-30, 12-20, 12-19, 12-18, 12-17, 12-16, 12-15, 12-14, or 12-13 amino acids) (e.g., 14-200, 16-200, 18-200, 20-200, 30-200, 40-200, 50-200, 60-200, 70-200, 80-200, 90-200, 100-200, 120-200, 140-200, 160-200, 180-200, or 190- 200 amino acids). In some embodiments, a linker between t a gp41-binding peptide and an Fc domain monomer (e.g. L₁ or L₂) is polypeptide containing 12-30 amino acids (e.g., 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 amino acids). Suitable peptide linkers are known in the art, and include, for example, peptide linkers containing flexible amino acid residues such as glycine and serine. In certain embodiments, a linker can contain motifs, e.g., multiple or repeating motifs, of GS, GGS, GGGGS (SEQ ID NO: 95), GGSG (SEQ ID NO: 96), or SGGG (SEQ ID NO: 97). In certain embodiments, a linker can contain 2 to 12 amino acids including motifs of GS, e.g., GS, GSGS (SEQ ID NO: 98), GSGSGS (SEQ ID NO: 99), GSGSGSGS (SEQ ID NO: 100), GSGSGSGSGS (SEQ ID NO: 101), or GSGSGSGSGSGS (SEQ ID NO: 102). In certain other embodiments, a linker can contain 3 to 12 amino acids including motifs of GGS, e.g., GGS, GGSGGS (SEQ ID NO: 103), GGSGGSGGS (SEQ ID NO: 104), and GGSGGSGGSGGS (SEQ ID NO: 105). In yet other embodiments, a linker can contain 4 to 12 amino acids including motifs of GGSG (SEQ ID NO: 106), e.g., GGSGGGSG (SEQ ID NO: 107), or GGSGGGSGGGSG (SEQ ID NO: 108). In other embodiments, a linker can contain motifs of GGGGS (SEQ ID NO: 109), e.g., GGGGSGGGGSGGGGS (SEQ ID NO: 110). In certain embodiments, a linker is SGGGSGGGSGGGSGGGSGGG (SEQ ID NO: 111). In preferred embodiments, a peptide linker (e.g., L₁ and L₂) is a peptide linker including the amino acid sequence of any one of (GS)x, (GGS)x, (GGGGS)x, (GGSG)x, (SGGG)x, wherein x is an integer from 1 to 50 (e.g., 1-40, 1-30, 1-20, 1-10, or 1-5). In some embodiments, a peptide linker contains only glycine residues, e.g., at least 4 glycine residues (e.g., 4-200, 4-180, 4-160, 4-140, 4-40, 4-100, 4-90, 4-80, 4-70, 4-60, 4-50, 4-40, 4-30, 4-20, 4- 19, 4-18, 4-17, 4-16, 4-15, 4-14, 4-13, 4-12, 4-11, 4-10, 4-9, 4-8, 4-7, 4-6 or 4-5 glycine residues) (e.g., 4- 200, 6-200, 8-200, 10-200, 12-200, 14-200, 16-200, 18-200, 20-200, 30-200, 40-200, 50-200, 60-200, 70- 200, 80-200, 90-200, 100-200, 120-200, 140-200, 160-200, 180-200, or 190-200 glycine residues). In certain embodiments, a linker has 4-30 glycine residues (e.g., 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, or 30 glycine residues). In some embodiments, a linker containing only glycine residues may not be glycosylated (e.g., O-linked glycosylation, also referred to as O-glycosylation) or may have a decreased level of glycosylation (e.g., a decreased level of O- glycosylation) (e.g., a decreased level of O-glycosylation with glycans such as xylose, mannose, sialic acids, fucose (Fuc), and/or galactose (Gal) (e.g., xylose)) as compared to, e.g., a linker containing one or more serine residues. In some embodiments, a linker containing only glycine residues may not be O-glycosylated (e.g., O-xylosylation) or may have a decreased level of O-glycosylation (e.g., a decreased level of O- xylosylation) as compared to, e.g., a linker containing one or more serine residues. In some embodiments, a linker containing only glycine residues may not undergo proteolysis or may have a decreased rate of proteolysis as compared to, e.g., a linker containing one or more serine residues. In certain embodiments, a linker can contain motifs of GGGG (SEQ ID NO: 112), e.g., GGGGGGGG (SEQ ID NO: 113), GGGGGGGGGGGG (SEQ ID NO: 114), GGGGGGGGGGGGGGGG (SEQ ID NO: 115), or GGGGGGGGGGGGGGGGGGGG (SEQ ID NO: 116). In certain embodiments, a linker can contain motifs of GGGGG (SEQ ID NO: 117), e.g., GGGGGGGGGG (SEQ ID NO: 118), GGGGGGGGGGGGGGG (SEQ ID NO: 119), or GGGGGGGGGGGGGGGGGGGG (SEQ ID NO: 120). In certain embodiments, a linker is GGGGGGGGGGGGGGGGGGGG (SEQ ID NO: 121). In other embodiments, a linker can also contain amino acids other than glycine and serine, e.g., GENLYFQSGG (SEQ ID NO: 122), SACYCELS (SEQ ID NO: 123), RSIAT (SEQ ID NO: 124), RPACKIPNDLKQKVMNH (SEQ ID NO: 125), GGSAGGSGSGSSGGSSGASGTGTAGGTGSGSGTGSG (SEQ ID NO: 126), AAANSSIDLISVPVDSR (SEQ ID NO: 127), or GGSGGGSEGGGSEGGGSEGGGSEGGGSEGGGSGGGS (SEQ ID NO: 128). Chemical linkers In some embodiments, a linker provides space, rigidity, and/or flexibility between two or more components of the fusion protein or conjugate. In some embodiments, a linker may be a bond, e.g., a covalent bond, e.g., an amide bond, a disulfide bond, a C-O bond, a C-N bond, a N-N bond, a C-S bond, or any kind of bond created from a chemical reaction, e.g., chemical conjugation. In some embodiments, a linker includes no more than 250 atoms (e.g., 1-2, 1-4, 1-6, 1-8, 1-10, 1-12, 1-14, 1-16, 1-18, 1-20, 1-25, 1-30, 1-35, 1-40, 1-45, 1-50, 1-55, 1-60, 1-65, 1-70, 1-75, 1-80, 1-85, 1-90, 1-95, 1-100, 1-110, 1-120, 1- 130, 1-140, 1-150, 1-160, 1-170, 1-180, 1-190, 1-200, 1-210, 1-220, 1-230, 1-240, or 1-250 atom(s); 250, 240, 230, 220, 210, 200, 190, 180, 170, 160, 150, 140, 130, 120, 110, 100, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 28, 26, 24, 22, 20, 18, 16, 14, 12, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 atom(s)). In some embodiments, a linker includes no more than 250 non-hydrogen atoms (e.g., 1-2, 1-4, 1-6, 1-8, 1-10, 1- 12, 1-14, 1-16, 1-18, 1-20, 1-25, 1-30, 1-35, 1-40, 1-45, 1-50, 1-55, 1-60, 1-65, 1-70, 1-75, 1-80, 1-85, 1- 90, 1-95, 1-100, 1-110, 1-120, 1-130, 1-140, 1-150, 1-160, 1-170, 1-180, 1-190, 1-200, 1-210, 1-220, 1- 230, 1-240, or 1-250 non-hydrogen atom(s); 250, 240, 230, 220, 210, 200, 190, 180, 170, 160, 150, 140, 130, 120, 110, 100, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 28, 26, 24, 22, 20, 18, 16, 14, 12, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 non-hydrogen atom(s)). In some embodiments, the backbone of a linker includes no more than 250 atoms (e.g., 1-2, 1-4, 1-6, 1-8, 1-10, 1-12, 1-14, 1-16, 1-18, 1-20, 1-25, 1-30, 1-35, 1-40, 1-45, 1-50, 1-55, 1-60, 1-65, 1-70, 1-75, 1-80, 1-85, 1-90, 1-95, 1-100, 1-110, 1-120, 1-130, 1- 140, 1-150, 1-160, 1-170, 1-180, 1-190, 1-200, 1-210, 1-220, 1-230, 1-240, or 1-250 atom(s); 250, 240, 230, 220, 210, 200, 190, 180, 170, 160, 150, 140, 130, 120, 110, 100, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 28, 26, 24, 22, 20, 18, 16, 14, 12, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 atom(s)). The “backbone” of a linker refers to the atoms in the linker that together form the shortest path from one part of the conjugate to another part of the conjugate. The atoms in the backbone of the linker are directly involved in linking one part of the conjugate to another part of the conjugate. For examples, hydrogen atoms attached to carbons in the backbone of the linker are not considered as directly involved in linking one part of the conjugate to another part of the conjugate. Molecules that may be used to make linkers include at least two functional groups, e.g., two carboxylic acid groups. In some embodiments of a divalent linker, the divalent linker may contain two carboxylic acids, in which the first carboxylic acid may form a covalent linkage with one component in the conjugate and the second carboxylic acid may form a covalent linkage (e.g., a C-S bond or a C-N bond) with another component in the conjugate. In some embodiments, dicarboxylic acid molecules may be used as linkers (e.g., a dicarboxylic acid linker). Examples of dicarboxylic acids molecules that may be used to form linkers include, but are not limited to,

wherein n is an integer from 1 to 20 (e.g., n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20). Other examples of dicarboxylic acids molecules that may be used to form linkers include, but are not limited to,

In some embodiments, dicarboxylic acid molecules, such as the ones described herein, may be further functionalized to contain one or more additional functional groups. In some embodiments, the linking group may comprise a moiety comprising a carboxylic acid moiety and an amino moiety that are spaced by from 1 to 25 atoms. Examples of such linking groups include, but are not limited to,

wherein n is an integer from 1 to 20 (e.g., n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20). In some embodiments, a linking group may including a moiety including a carboxylic acid moiety and an amino moiety, such as the ones described herein, may be further functionalized to contain one or more additional functional groups. Such linking groups may be further functionalized, for example, to provide an attachment point to an Fc domain monomer or a gp41-binding peptide (e.g., by way of a linker, such as a PEG linker). In some embodiments, the linking group may comprise a moiety comprising two or amino moieties (e.g., a diamino moiety) that are spaced by from 1 to 25 atoms. Examples of such linking groups include, but are not limited to,

wherein n is an integer from 1 to 20 (e.g., n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20). In some embodiments, a linking group may include a diamino moiety, such as the ones described herein, may be further functionalized to contain one or more additional functional groups. Such diamino linking groups may be further functionalized, for example, to provide an attachment point to an Fc domain monomer or a gp41-binding peptide (e.g., by way of a linker, such as a PEG linker). In some embodiments, a molecule containing an azide group may be used to form a linker, in which the azide group may undergo cycloaddition with an alkyne to form a 1,2,3-triazole linkage. In some embodiments, a molecule containing an alkyne group may be used to form a linker, in which the alkyne group may undergo cycloaddition with an azide to form a 1,2,3-triazole linkage. In some embodiments, a molecule containing a maleimide group may be used to form a linker, in which the maleimide group may react with a cysteine to form a C-S linkage. In some embodiments, a molecule containing one or more ^{haloalkyl groups may be used to form a linker, in which the haloalkyl group may form a covalent linkage,} e.g., C-N and C-O linkage. In some embodiments, a linker may comprise a synthetic group derived from, e.g., a synthetic polymer (e.g., a polyethylene glycol (PEG) polymer). In some embodiments, a linker may comprise one or more amino acid residues. In some embodiments, a linker may be an amino acid sequence (e.g., a 1- 25 amino acid, 1-10 amino acid, 1-9 amino acid, 1-8 amino acid, 1-7 amino acid, 1-6 amino acid, 1-5 amino acid, 1-4 amino acid, 1-3 amino acid, 1-2 amino acid, or 1 amino acid sequence). In some embodiments, a linker (L or L’) may include one or more optionally substituted C1-C20 alkylene, optionally substituted C1-C20 heteroalkylene (e.g., a PEG unit), optionally substituted C₂-C₂₀ alkenylene (e.g., C2 alkenylene), optionally substituted C₂-C₂₀ heteroalkenylene, optionally substituted C₂-C₂₀ alkynylene, optionally substituted C₂-C₂₀ heteroalkynylene, optionally substituted C3-C20 cycloalkylene (e.g., cyclopropylene, cyclobutylene), optionally substituted C2-C20 heterocycloalkylene, optionally substituted C4-C20 cycloalkenylene, optionally substituted C4-C20 heterocycloalkenylene, optionally substituted C8-C20 cycloalkynylene, optionally substituted C8-C20 heterocycloalkynylene, optionally substituted C5-C15 arylene (e.g., C6 arylene), optionally substituted C3-C15 heteroarylene (e.g., imidazole, pyridine), O, S, NRⁱ (Rⁱ is H, optionally substituted C1-C20 alkyl, optionally substituted C1-C20 heteroalkyl, optionally substituted C₂-C₂₀ alkenyl, optionally substituted C₂-C₂₀ heteroalkenyl, optionally substituted C₂-C₂₀ alkynyl, optionally substituted C₂-C₂₀ heteroalkynyl, optionally substituted C3-C20 cycloalkyl, optionally substituted C2-C20 heterocycloalkyl, optionally substituted C4-C20 cycloalkenyl, optionally substituted C4-C20 heterocycloalkenyl, optionally substituted C8-C20 cycloalkynyl, optionally substituted C8-C20 heterocycloalkynyl, optionally substituted C5-C15 aryl, or optionally substituted C3-C15 heteroaryl), P, carbonyl, thiocarbonyl, sulfonyl, phosphate, phosphoryl, or imino. Conjugation chemistries Covalent conjugation of two or more components in a conjugate using a linker may be accomplished using well-known organic chemical synthesis techniques and methods. Complementary functional groups on two components may react with each other to form a covalent bond. Examples of complementary reactive functional groups include, but are not limited to, e.g., maleimide and cysteine, amine and activated carboxylic acid, thiol and maleimide, activated sulfonic acid and amine, isocyanate and amine, azide and alkyne, and alkene and tetrazine. Site-specific conjugation to a polypeptide may accomplished using techniques known in the art. Exemplary techniques for site-specific conjugation to an Fc domain are provided in Agarwall. P., et al. Bioconjugate Chem.26:176-192 (2015). Other examples of functional groups capable of reacting with amino groups include, e.g., alkylating and acylating agents. Representative alkylating agents include: (i) an α-haloacetyl group, e.g., XCH2CO- (where X=Br, Cl, or I); (ii) a N-maleimide group, which may react with amino groups either through a Michael type reaction or through acylation by addition to the ring carbonyl group; (iii) an aryl halide, e.g., a nitrohaloaromatic group; (iv) an alkyl halide; (v) an aldehyde or ketone capable of Schiff’s base formation with amino groups; (vi) an epoxide, e.g., an epichlorohydrin and a bisoxirane, which may react with amino, sulfhydryl, or phenolic hydroxyl groups; (vii) a chlorine-containing of s-triazine, which is reactive towards nucleophiles such as amino, sufhydryl, and hydroxyl groups; (viii) an aziridine, which is reactive towards nucleophiles such as amino groups by ring opening; (ix) a squaric acid diethyl ester; and (x) an α-haloalkyl ether. Examples of amino-reactive acylating groups include, e.g., (i) an isocyanate and an isothiocyanate; (ii) a sulfonyl chloride; (iii) an acid halide; (iv) an active ester, e.g., a nitrophenylester or N- hydroxysuccinimidyl ester; (v) an acid anhydride, e.g., a mixed, symmetrical, or N-carboxyanhydride; (vi) an acylazide; and (vii) an imidoester. Aldehydes and ketones may be reacted with amines to form Schiff’s bases, which may be stabilized through reductive amination. It will be appreciated that certain functional groups may be converted to other functional groups prior to reaction, for example, to confer additional reactivity or selectivity. Examples of methods useful for this purpose include conversion of amines to carboxyls using reagents such as dicarboxylic anhydrides; conversion of amines to thiols using reagents such as N-acetylhomocysteine thiolactone, S- acetylmercaptosuccinic anhydride, 2-iminothiolane, or thiol-containing succinimidyl derivatives; conversion of thiols to carboxyls using reagents such as α -haloacetates; conversion of thiols to amines using reagents such as ethylenimine or 2-bromoethylamine; conversion of carboxyls to amines using reagents such as carbodiimides followed by diamines; and conversion of alcohols to thiols using reagents such as tosyl chloride followed by transesterification with thioacetate and hydrolysis to the thiol with sodium acetate. In some embodiments, a linker of the invention, is conjugated (e.g., by any of the methods described herein) to a fusion protein, for example the Fc portion of a fusion protein. In some embodiments of the invention, the linker is conjugated by way of: (a) a thiourea linkage (i.e., - NH(C=S)NH-) to a lysine; (b) a carbamate linkage (i.e., -NH(C=O)-O) to a lysine; (c) an amine linkage by reductive amination (i.e., -NHCH2) to a lysine; (d) an amide (i.e., -NH-(C=O)CH2) to a lysine; (e) a cysteine-maleimide conjugate between a maleimide of the linker to a cysteine; (f) an amine linkage by reductive amination (i.e., -NHCH2) between the linker and a carbohydrate (e.g., a glycosyl group of an Fc domain monomer or an Fc domain); (g) a rebridged cysteine conjugate, wherein the linker is conjugated to two cysteines; (h) an oxime linkage between the linker and a carbohydrate (e.g., a glycosyl group of an Fc domain monomer or an Fc domain); (i) an oxime linkage between the linker and an amino acid residue; (j) an azido linkage between the linker; (k) direct acylation of a linker; or (l) a thioether linkage between the linker. VI. Combination therapies Antiviral Agents In some embodiments, one or more antiviral agents may be administered in combination (e.g., administered substantially simultaneously (e.g., in the same pharmaceutical composition or in separate pharmaceutical compositions) or administered separately at different times) with a fusion protein or a conjugate described herein. In some embodiments, the antiviral agent is an antiviral agent for the treatment of HIV. For example, the antiviral agent may be a nucleoside/nucleotide reverse transcriptase inhibitor, a gp120 inhibitor, a polymerase inhibitor, or a fusion protein inhibitor. The antiviral agent may target either the virus or the host subject. The antiviral agent for the treatment of HIV used in combination with a fusion protein or a conjugate described herein may be selected from an integrase inhibitor (e.g., dolutegravir, elvitegravir, or raltegravir), a nucleoside reverse transcriptase inhibitor (NRTI) (e.g., abacavir, lamivudine, zidovudine, emtricitabine, tenofovir, emtricitabine, didanosine, or stavudine), a non-nucleoside reverse transcriptase inhibitor (NNRTI) (e.g., efavirenz, etravirine, nevirapine, rilpivirine, or delavirdine), a protease inhibitor (e.g., atazanavir, cobicistat, darunavir, cobicistat, lopinavir, ritonavir, fosamprenavir, tipranavir, nelfinavir, indinavir, or saquinavir), an inhibitor of viral entry (e.g., enfuvirtide), a CCR5 antagonist (e.g., maraviroc), or a CYP3A inhibitor (e.g., cobicistat or ritonavir), or an siRNA targeting a host or viral gene, or prodrugs thereof, or pharmaceutically acceptable salts thereof. Antiviral vaccines In some embodiments, any one of the fusion proteins or conjugates described herein is administered in combination with an antiviral vaccine (e.g., a composition that elicits an immune response in a subject directed against a virus). The antiviral vaccine may be administered substantially simultaneously (e.g., in the same pharmaceutical composition or in separate pharmaceutical compositions) as the conjugates, or may be administered prior to or following the fusion protein or conjugate (e.g., within a period of 1 day, 2, days, 5, days, 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 6 months, or 12 months, or more). In some embodiments the viral vaccine includes an immunogen that elicits an immune response in the subject against HIV-1 or HIV-2. In some embodiments the vaccine is administered as a nasal spray. VII. Methods Methods described herein include, e.g., methods of protecting against or treating a viral infection (e.g., an HIV infection) in a subject and methods of preventing, stabilizing, or inhibiting the growth of viral particles. A method of treating a viral infection (e.g., an HIV infection) in a subject includes administering to the subject a fusion protein or a conjugate described herein or a pharmaceutical composition thereof. In some embodiments, the viral infection is cause by the human immunodeficiency virus (e.g., HIV-1 or HIV-2). In some embodiments, the viral infection is caused by a resistant strain of virus. A method of preventing, stabilizing, or inhibiting the growth of viral particles or preventing the replication and spread of the virus includes contacting the virus or a site susceptible to viral growth with a fusion protein or a conjugate described herein or a pharmaceutical composition thereof. Moreover, methods described herein also include methods of protecting against or treating viral infection in a subject by administering to the subject a fusion protein or a conjugate described herein. In some embodiments, the method further includes administering to the subject an antiviral agent or an antiviral vaccine. Methods described herein also include methods of protecting against or treating a viral infection in a subject by administering to said subject (1) a fusion protein or a conjugate described herein and (2) an antiviral agent or an antiviral vaccine. Methods described herein also include methods of preventing, stabilizing, or inhibiting the growth of viral particles or preventing the replication or spread of a virus, by contacting the virus or a site susceptible to viral growth with (1) a fusion protein or conjugate described herein and (2) an antiviral agent or an antiviral vaccine. In some embodiments, the fusion protein or conjugate described herein is administered first, followed by administering of the antiviral agent or antiviral vaccine alone. In some embodiments, the antiviral agent or antiviral vaccine is administered first, followed by administering of the fusion protein or conjugate described herein alone. In some embodiments, the fusion protein or conjugate described herein and the antiviral agent or antiviral vaccine are administered substantially simultaneously (e.g., in the same pharmaceutical composition or in separate pharmaceutical compositions). In some embodiments, the fusion protein or conjugate described herein or the antiviral agent or antiviral vaccine is administered first, followed by administering of the conjugate described herein and the antiviral agent or antiviral vaccine substantially simultaneously (e.g., in the same pharmaceutical composition or in separate pharmaceutical compositions). In some embodiments, the fusion protein or conjugate described herein and the antiviral agent or antiviral vaccine are administered first substantially simultaneously (e.g., in the same pharmaceutical composition or in separate pharmaceutical compositions), followed by administering of the fusion protein or conjugate described herein or the antiviral agent or antiviral vaccine alone. In some embodiments, when a fusion protein or conjugate described herein and an antiviral agent or antiviral vaccine are administered together (e.g., substantially simultaneously in the same or separate pharmaceutical compositions, or separately in the same treatment regimen), inhibition of viral replication of each of the fusion protein or conjugate and the antiviral agent or antiviral vaccine may be greater (e.g., occur at a lower concentration) than inhibition of viral replication of each of the fusion protein or conjugate and the antiviral agent or antiviral vaccine when each is used alone in a treatment regimen. VIII. Pharmaceutical Compositions and Preparations A fusion protein or a conjugate described herein may be formulated in a pharmaceutical composition for use in the methods described herein. In some embodiments, a fusion protein or a conjugate described herein may be formulated in a pharmaceutical composition alone. In some embodiments, a fusion protein or a conjugate described herein may be formulated in combination with an antiviral agent or antiviral vaccine in a pharmaceutical composition. In some embodiments, the pharmaceutical composition includes a fusion protein or a conjugate described herein and one or more pharmaceutically acceptable carriers or excipients. Acceptable carriers and excipients in the pharmaceutical compositions are nontoxic to recipients at the dosages and concentrations employed. Acceptable carriers and excipients may include buffers such as phosphate, citrate, HEPES, and TAE, antioxidants such as ascorbic acid and methionine, preservatives such as hexamethonium chloride, octadecyldimethylbenzyl ammonium chloride, resorcinol, and benzalkonium chloride, proteins such as human serum albumin, gelatin, dextran, and immunoglobulins, hydrophilic polymers such as polyvinylpyrrolidone, amino acid residues such as glycine, glutamine, histidine, and lysine, and carbohydrates such as glucose, mannose, sucrose, and sorbitol. Examples of other excipients include, but are not limited to, antiadherents, binders, coatings, compression aids, disintegrants, dyes, emollients, emulsifiers, fillers (diluents), film formers or coatings, flavors, fragrances, glidants (flow enhancers), lubricants, sorbents, suspensing or dispersing agents, or sweeteners. Exemplary excipients include, but are not limited to: butylated hydroxytoluene (BHT), calcium carbonate, calcium phosphate (dibasic), calcium stearate, croscarmellose, crosslinked polyvinyl pyrrolidone, citric acid, crospovidone, cysteine, ethylcellulose, gelatin, hydroxypropyl cellulose, hydroxypropyl methylcellulose, lactose, magnesium stearate, maltitol, mannitol, methionine, methylcellulose, methyl paraben, microcrystalline cellulose, polyethylene glycol, povidone, pregelatinized starch, propyl paraben, retinyl palmitate, shellac, silicon dioxide, sodium carboxymethyl cellulose, sodium citrate, sodium starch glycolate, sorbitol, starch (corn), stearic acid, stearic acid, sucrose, talc, titanium dioxide, vitamin A, vitamin E, vitamin C, and xylitol. The fusion proteins or conjugates herein may have ionizable groups so as to be capable of preparation as pharmaceutically acceptable salts. These salts may be acid addition salts involving inorganic or organic acids or the salts may, in the case of acidic forms of the conjugates herein be prepared from inorganic or organic bases. Frequently, the fusion proteins or conjugates are prepared or used as pharmaceutically acceptable salts prepared as addition products of pharmaceutically acceptable acids or bases. Suitable pharmaceutically acceptable acids and bases are well-known in the art, such as hydrochloric, sulphuric, hydrobromic, acetic, lactic, citric, or tartaric acids for forming acid addition salts, and potassium hydroxide, sodium hydroxide, ammonium hydroxide, caffeine, various amines, and the like for forming basic salts. Methods for preparation of the appropriate salts are well-established in the art. Representative acid addition salts include, but are not limited to, acetate, adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptonate, glycerophosphate, hemisulfate, heptonate, hexanoate, hydrobromide, hydrochloride, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, toluenesulfonate, undecanoate, and valerate salts. Representative alkali or alkaline earth metal salts include, but are not limited to, sodium, lithium, potassium, calcium, and magnesium, as well as nontoxic ammonium, quaternary ammonium, and amine cations, including, but not limited to ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, and ethylamine. Depending on the route of administration and the dosage, a fusion protein, a conjugate, or a pharmaceutical composition thereof used in the methods described herein will be formulated into suitable pharmaceutical compositions to permit facile delivery. A fusion protein or conjugate or a pharmaceutical composition thereof may be formulated to be administered intramuscularly, intravenously (e.g., as a sterile solution and in a solvent system suitable for intravenous use), intradermally, intraarterially, intraperitoneally, intralesionally, intracranially, intraarticularly, intraprostatically, intrapleurally, intratracheally, intranasally, intravitreally, intravaginally, intrarectally, topically, intratumorally, peritoneally, subcutaneously, subconjunctival, intravesicularlly, mucosally, intrapericardially, intraumbilically, intraocularally, orally (e.g., a tablet, capsule, caplet, gel cap, or syrup), topically (e.g., as a cream, gel, lotion, or ointment), locally, by inhalation, by injection, or by infusion (e.g., continuous infusion, localized perfusion bathing target cells directly, catheter, lavage, in cremes, or lipid compositions). Depending on the route of administration, a fusion protein or conjugate herein or a pharmaceutical composition thereof may be in the form of, e.g., tablets, capsules, pills, powders, granulates, suspensions, emulsions, solutions, gels including hydrogels, pastes, ointments, creams, plasters, drenches, osmotic delivery devices, suppositories, enemas, injectables, implants, sprays, preparations suitable for iontophoretic delivery, or aerosols. The compositions may be formulated according to conventional pharmaceutical practice. A fusion protein or conjugate described herein may be formulated in a variety of ways that are known in the art. For use as treatment of human and animal subjects, a fusion protein or conjugate described herein can be formulated as pharmaceutical or veterinary compositions. Depending on the subject (e.g., a human) to be treated, the mode of administration, and the type of treatment desired, e.g., prophylaxis or therapy, a conjugate described herein is formulated in ways consonant with these parameters. A summary of such techniques is found in Remington: The Science and Practice of Pharmacy, 22nd Edition, Lippincott Williams & Wilkins (2012); and Encyclopedia of Pharmaceutical Technology, 4th Edition, J. Swarbrick and J. C. Boylan, Marcel Dekker, New York (2013), each of which is incorporated herein by reference. Formulations may be prepared in a manner suitable for systemic administration or topical or local administration. Systemic formulations include those designed for injection (e.g., intramuscular, intravenous or subcutaneous injection) or may be prepared for transdermal, transmucosal, or oral administration. The formulation will generally include a diluent as well as, in some cases, adjuvants, buffers, and preservatives. The conjugates can be administered also in liposomal compositions or as microemulsions. Systemic administration may also include relatively noninvasive methods such as the use of suppositories, transdermal patches, transmucosal delivery and intranasal administration. Oral administration is also suitable for conjugates herein. Suitable forms include syrups, capsules, and tablets, as is understood in the art. The pharmaceutical compositions can be administered parenterally in the form of an injectable formulation. Pharmaceutical compositions for injection can be formulated using a sterile solution or any pharmaceutically acceptable liquid as a vehicle. Formulations may be prepared as solid forms suitable for solution or suspension in liquid prior to injection or as emulsions. Pharmaceutically acceptable vehicles include, but are not limited to, sterile water, physiological saline, and cell culture media (e.g., Dulbecco’s Modified Eagle Medium (DMEM), α-Modified Eagles Medium (α-MEM), F-12 medium). Such injectable compositions may also contain amounts of nontoxic auxiliary substances such as wetting or emulsifying agents, pH buffering agents, such as sodium acetate and sorbitan monolaurate. Formulation methods are known in the art, see e.g., Pharmaceutical Preformulation and Formulation, 2nd Edition, M. Gibson, Taylor & Francis Group, CRC Press (2009). The pharmaceutical compositions can be prepared in the form of an oral formulation. Formulations for oral use include tablets containing the active ingredient(s) in a mixture with non-toxic pharmaceutically acceptable excipients. These excipients may be, for example, inert diluents or fillers (e.g., sucrose, sorbitol, sugar, mannitol, microcrystalline cellulose, starches including potato starch, calcium carbonate, sodium chloride, lactose, calcium phosphate, calcium sulfate, or sodium phosphate); granulating and disintegrating agents (e.g., cellulose derivatives including microcrystalline cellulose, starches including potato starch, croscarmellose sodium, alginates, or alginic acid); binding agents (e.g., sucrose, glucose, sorbitol, acacia, alginic acid, sodium alginate, gelatin, starch, pregelatinized starch, microcrystalline cellulose, magnesium aluminum silicate, carboxymethylcellulose sodium, methylcellulose, hydroxypropyl methylcellulose, ethylcellulose, polyvinylpyrrolidone, or polyethylene glycol); and lubricating agents, glidants, and antiadhesives (e.g., magnesium stearate, zinc stearate, stearic acid, silicas, hydrogenated vegetable oils, or talc). Formulations for oral use may also be provided as chewable tablets, or as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent (e.g., potato starch, lactose, microcrystalline cellulose, calcium carbonate, calcium phosphate or kaolin), or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, for example, peanut oil, liquid paraffin, or olive oil. Powders, granulates, and pellets may be prepared using the ingredients mentioned above under tablets and capsules in a conventional manner using, e.g., a mixer, a fluid bed apparatus or a spray drying equipment. Other pharmaceutically acceptable excipients for oral formulations include, but are not limited to, colorants, flavoring agents, plasticizers, humectants, and buffering agents. Formulations for oral use may also be provided as chewable tablets, or as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent (e.g., potato starch, lactose, microcrystalline cellulose, calcium carbonate, calcium phosphate or kaolin), or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, for example, peanut oil, liquid paraffin, or olive oil. Powders, granulates, and pellets may be prepared using the ingredients mentioned above under tablets and capsules in a conventional manner using, e.g., a mixer, a fluid bed apparatus or a spray drying equipment. Dissolution or diffusion controlled release of a fusion protein or conjugate described herein or a pharmaceutical composition thereof can be achieved by appropriate coating of a tablet, capsule, pellet, or granulate formulation of the conjugate, or by incorporating the conjugate into an appropriate matrix. A controlled release coating may include one or more of the coating substances mentioned above and/or, e.g., shellac, beeswax, glycowax, castor wax, carnauba wax, stearyl alcohol, glyceryl monostearate, glyceryl distearate, glycerol palmitostearate, ethylcellulose, acrylic resins, dl-polylactic acid, cellulose acetate butyrate, polyvinyl chloride, polyvinyl acetate, vinyl pyrrolidone, polyethylene, polymethacrylate, methylmethacrylate, 2-hydroxymethacrylate, methacrylate hydrogels, 1,3 butylene glycol, ethylene glycol methacrylate, and/or polyethylene glycols. In a controlled release matrix formulation, the matrix material may also include, e.g., hydrated methylcellulose, carnauba wax and stearyl alcohol, carbopol 934, silicone, glyceryl tristearate, methyl acrylate-methyl methacrylate, polyvinyl chloride, polyethylene, and/or halogenated fluorocarbon. The pharmaceutical composition may be formed in a unit dose form as needed. The amount of active component, e.g., a fusion protein or a conjugate described herein, included in the pharmaceutical compositions are such that a suitable dose within the designated range is provided (e.g., a dose within the range of 0.01-100 mg/kg of body weight). IX. Routes of Administration and Dosages In any of the methods described herein, fusion proteins or conjugates herein may be administered by any appropriate route for treating or protecting against a viral infection (e.g., an HIV infection), or for preventing, stabilizing, or inhibiting the proliferation or spread of a virus (e.g., an HIV virus). Fusion protein or conjugates described herein may be administered to humans, domestic pets, livestock, or other animals with a pharmaceutically acceptable diluent, carrier, or excipient. In some embodiments, administering includes administration of any of the fusion proteins or conjugates described herein or compositions intramuscularly, intravenously (e.g., as a sterile solution and in a solvent system suitable for intravenous use), intradermally, intraarterially, intraperitoneally, intralesionally, intracranially, intraarticularly, intraprostatically, intrapleurally, intratracheally, intranasally, intravitreally, intravaginally, intrarectally, topically, intratumorally, peritoneally, subcutaneously, subconjunctival, intravesicularlly, mucosally, intrapericardially, intraumbilically, intraocularally, orally (e.g., a tablet, capsule, caplet, gelcap, or syrup), topically (e.g., as a cream, gel, lotion, or ointment), locally, by inhalation, by injection, or by infusion (e.g., continuous infusion, localized perfusion bathing target cells directly, catheter, lavage, in cremes, or lipid compositions). In some embodiments, if an antiviral agent is also administered in addition to a conjugate described herein, the antiviral agent or a pharmaceutical composition thereof may also be administered in any of the routes of administration described herein. The dosage of a fusion protein or conjugate described herein or pharmaceutical compositions thereof depends on factors including the route of administration, the disease to be treated (e.g., the extent and/or condition of the viral infection), and physical characteristics, e.g., age, weight, general health, of the subject. Typically, the amount of the conjugate or the pharmaceutical composition thereof contained within a single dose may be an amount that effectively prevents, delays, or treats the viral infection without inducing significant toxicity. A pharmaceutical composition may include a dosage of a fusion protein or conjugate described herein ranging from 0.01 to 500 mg/kg (e.g., 0.01, 0.1, 0.2, 0.3, 0.4, 0.5, 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 mg/kg) and, in a more specific embodiment, about 0.1 to about 30 mg/kg and, in a more specific embodiment, about 1 to about 30 mg/kg. In some embodiments, when a fusion protein or conjugate described herein and an antiviral agent or antiviral vaccine are administered in combination (e.g., substantially simultaneously in the same or separate pharmaceutical compositions, or separately in the same treatment regimen), the dosage needed of the fusion protein or conjugate described herein may be lower than the dosage needed of the fusion protein or conjugate if the fusion protein or conjugate was used alone in a treatment regimen. A fusion protein or conjugate described hereinor a pharmaceutical composition thereof may be administered to a subject in need thereof, for example, one or more times (e.g., 1-10 times or more; 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 times) daily, weekly, monthly, biannually, annually, or as medically necessary. Dosages may be provided in either a single or multiple dosage regimens. The timing between administrations may decrease as the medical condition improves or increase as the health of the patient declines. The dosage and frequency of administration may be adapted by the physician in accordance with conventional factors such as the extent of the infection and different parameters of the subject. EXAMPLES The following examples are put forth so as to provide those of ordinary skill in the art with a description of how the compositions and methods described herein may be used, made, and evaluated, and are intended to be purely exemplary of the invention and are not intended to limit the scope of what the inventors regard as their invention. Example 1. 30-day comparative non-human primate PK study following IV administration of a conjugate including an Fc domain having a C220S single mutation and a C220S/YTE quadruple mutation Conjugates having an Fc domain decorated with one or more small molecule inhibitors of HIV were synthesized. The conjugates either included an Fc domain having a C220S YTE quadruple mutation (SEQ ID NO: 67) or an Fc domain having only a C220S single mutation (SEQ ID NO: 64). A non-human primate PK study was performed to compare IV administration of the C220S/YTE Fc conjugate to the C220S Fc conjugate. The PK performance results described herein are expected to extend to a conjugate of an Fc domain with a gp41-inhibiting peptide such as any of the conjugates described herein. Non-human primate (NHP) PK studies were performed by BTS Research (San Diego, CA) using male and female cynomolgus monkeys 5-9 years old with body weights ranging from 3.5-8.5 kg. NHPs were injected IV with 2 mg/kg of test article (0.4 mL/kg dose volume). Animals were housed under standard IACUC approved housing conditions. At appropriate times animals were non-terminally bled (via femoral or cephalic veins) with blood collected in K2EDTA tubes to prevent coagulation. Collected blood was centrifuged (2,000 x g, for 10 minutes) and plasma withdrawn for analysis of test article concentrations over time. The plasma concentrations for the C220S/YTE Fc conjugate and the C220S conjugate at each time point were measured by sandwich ELISA. Briefly, test articles were captured on Fc-coated plates and then detected using a HRP-conjugated anti-human IgG-Fc antibody. Protein concentrations were calculated in GraphPad Prism using 4PL non-linear regression of the C220S/YTE Fc conjugate or C220S conjugate standard curves. A more detailed method description is provided above. The corresponding curves are shown in FIG.2. The C220S/YTE Fc conjugate demonstrates a significantly improved terminal half-life of ~45 days compared with ~10 days for the C220S Fc conjugate. AUCs for the C220S/YTE Fc conjugate are 2X greater than the AUCs for The C220S conjugate (Table 3).

able 3. Monkey PK, C220S/YTE Fc conjugate vs. C220S Fc conjugate

Example 2. Fusion protein production Constructs were ordered from Genscript with the pcDNA3.1(+) plasmid backbone. Plasmids were transformed into TOP₁0 competent E. coli cells and plated on LB agar plates with carbenicillen. The colonies were inoculated in TB liquid cultures and incubated overnight. The cultures were harvested using the Invitrogen maxiprep kit and the eluted DNA was precipitated with isopropanol and washed with 70% ethanol to reduce endotoxin levels. CHO-S cells were transfected with the plasmid DNA using the ExpiCHO “Max titer” protocol from ThermoFisher. Cells were seeded at 6 x 10^6 cells/ml and transfected with a combination of plasmid DNA and lipofectamine. The transfected cultures were incubated at 8% CO2 and 37°C for 18 to 22 hours. Enhancers and feed were added to the cultures, which were then incubated at 5% CO2 and 32°C for 11 to 13 days. Additional feed is added on day 5. For protein harvest, cultures were spun down and the supernatant was filtered using 0.2 micron aPES filter. Supernatants were processed over Protein A (MabSelect PrismA) columns with a peristaltic pump, eluted with 0.1 M acetic acid 3.5 pH, and buffer exchanged into 1X PBS. A secondary purification step with size exclusion chromatography was used to remove aggregate. The protein was then filtered with a 0.2 micron Mustang E membrane and the quality was analyzed with SDS-PAGE (FIGS.3-6), MALDI, and analytical SEC. Data for protein production are shown below in Table 4. Table 4. Fusion protein production

Example 3. Screening of HIV compounds in an in vitro cell fusion assay Activity of HIV compounds was determined in an assay designed to measure the inhibition of cell- cell fusion mediated by gp120 and CD4 interaction which is an important step in the HIV infection process. Briefly, this assay measures the fusion of two cell lines, HeLa-CD4-LTR-β-Gal (catalog #1294) and HL₂/3 cells (catalog #1299), obtained from the AIDS Research Reagent and Reference Program (Rockville, MD). HeLa-CD4-LTR-β-Gal cells were plated at a density of 5 x 10³ cells per well in a volume of 50 µL, with 50 µL of nine serial half-logarithmic dilutions of compound in triplicate for one hour at 37 ºC/5% CO2. Following the incubation, 100 µL of HL₂/3 cells were added to the plates. The cultures were incubated for an additional 48 hours at 37 ºC/5% CO2. Following the incubation, efficacy plates were evaluated for β-galactosidase production using a chemiluminescent substrate and toxicity plates were stained with XTT to evaluate cell viability. In these studies, cytotoxicity was also evaluated (TC50). Test materials were derived by measuring the reduction of the tetrazolium dye XTT (2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5- [(phenylamino)carbonyl]-2H-tetrazolium hydroxide). XTT in metabolically active cells is metabolized by the mitochondrial enzyme NADPH oxidase to a soluble formazan product. XTT solution was prepared daily as a stock of 1 mg/mL in RPMI-1640 without additives. Phenazine methosulfate (PMS) solution was prepared at 0.15 mg/mL in DPBS and stored in the dark at -20 °C. XTT/PMS stock was prepared immediately before use by adding 40 µL of PMS per mL of XTT solution. Fifty µL (50 µL) of XTT/PMS was added to each well of the plate and the plate incubated for 4 hours at 37 °C. The 4 hour incubation has been empirically determined to be within the linear response range for XTT dye reduction with the indicated numbers of cells for each assay. The plates were sealed and inverted several times to mix the soluble formazan product and the plate was read at 450 nm (650 nm reference wavelength) with a Molecular Devices SpectraMax Plus 38496 well plate format spectrophotometer. In this assay 4 fusion proteins were run with 2 control compounds (Chicago Sky Blue (CSB) and Enfuvirtide) know to prevent cell fusion mediated by binding of viral gp120 to the host cell receptor (CD4) (Table 5). CSB and Enfuvirtide had EC50 values of 781 and 358 nM, indicating moderate inhibition of cell fusion. Importantly, fusion proteins tested were as potent or more potent than Enfuvirtide, with the exception of the fusion protein having an amino acid sequence of SEQ ID NO: 129. Lastly, no test articles showed cytotoxicity at the concentrations tested in this study. Table 5. Activity of selected compounds in a cell fusion assay (EC50) and cytotoxicity (TC50)

Claims

CLAIMS 1. A fusion protein comprising an Fc domain monomer conjugated to at least one glycoprotein 41 (gp41)-binding peptide.

2. The fusion protein of claim 1, comprising one Fc domain monomer conjugated to one gp41- binding peptide.

3. The fusion protein of claim 1, comprising one Fc domain monomer conjugated to two gp41- binding peptides.

4. The fusion protein of claim 1, comprising the structure: (P₂-L₂)n₂-B-(L₁-P₁)n₁ wherein B is an Fc domain monomer; P₁ and P₂ are each independently a gp41-binding peptide; L₁ and L₂ are each independently a linker; and n₁ and n₂ are each independently 0 or 1, wherein at least one of n₁ and n₂ is 1.

5. The fusion protein of claim 4, wherein n₁ is 1, n₂ is 0, and the fusion protein comprises the structure: B-L₁-P₁.

6. The fusion protein of claim 5, wherein the linker (L₁) is conjugated to C-terminus of the Fc domain monomer (B) and to the N-terminus of the gp41-binding peptide (P₁).

7. The fusion protein of claim 5, wherein the linker (L₁) is conjugated to N-terminus of the Fc domain monomer (B) and to the C-terminus of the gp41-binding peptide (P₁).

8. The fusion protein of any one of claims 5-7, wherein L₁ is a peptide linker comprising between 2 and 200 amino acids.

9. The fusion protein of claim 8, wherein L₁ is a peptide linker comprising between 5 and 25 amino acids.

10. The fusion protein of any one of claims 5-9, wherein L₁ is a peptide linker comprising the amino acid sequence of any one of (GS)x, (GGS)x, (GGGGS)x, (GGSG)x, (SGGG)x, wherein x is an integer from 1 to 10.

11. The fusion protein of any one of claims 5-10, wherein B, L₁, and P₁ are expressed as a single polypeptide chain.

12. The fusion protein of claim 5, wherein the linker (L₁) is conjugated to N-terminus of the Fc domain monomer (B) and to the N-terminus of the gp41-binding peptide (P₁).

13. The fusion protein of claim 5, wherein the linker (L₁) is conjugated to C-terminus of the Fc domain monomer (B) and to the C-terminus of the gp41-binding peptide (P₁).

14. The fusion protein of any one of claims 5-7, 12, or 13, wherein L₁ comprises a chemical linker that is covalently conjugated to each of B and P₁.

15. The fusion protein of any one of claims 5-7, 12, or 13, wherein B and P₁ are expressed as separate polypeptide chains and are subsequently each covalently conjugated to L₁.

16. The fusion protein of claim 4, wherein n₁ is 1, n₂ is 1, and the fusion protein comprises the structure: P₂-L₂-B-L₁-P₁.

17. The fusion protein of claim 16, wherein the linker (L₂) is conjugated to the C-terminus of the gp41-binding peptide (P₂) and to the N-terminus of the Fc domain monomer (B), and the linker (L₁) is conjugated to the C-terminus of the Fc domain monomer (B) and to the N-terminus of the gp41-binding peptide (P₁).

18. The fusion protein of claim 16 or 17, wherein L₁ and L₂ are each an independently selected peptide linker comprising between 2 and 200 amino acids.

19. The fusion protein of claim 18, wherein L₁ and L₂ are each an independently selected peptide linker comprising between 5 and 25 amino acids.

20. The fusion protein of any one of claims 16-19, wherein L₁ and L₂ are each an independently selected peptide linker comprising the amino acid sequence of any one of (GS)x, (GGS)x, (GGGGS)x, (GGSG)x, (SGGG)x, wherein x is an integer from 1 to 10.

21. The fusion protein of any one of claims 16-20, wherein P₂, L₂, B, L₁, and P₁ are expressed together as a single polypeptide chain.

22. The fusion protein of claim 16, wherein the linker (L₂) is conjugated to the N-terminus of the gp41-binding peptide (P₂) and to the N-terminus of the Fc domain monomer (B), and the linker (L₁) is conjugated to the N-terminus of the gp41-binding peptide (P₁) and to the C-terminus of the Fc domain monomer (B).

23. The fusion protein of claim 16, wherein the linker (L₂) is conjugated to the C-terminus of the gp41-binding peptide (P₂) and to the N-terminus of the Fc domain monomer (B), and the linker (L₁) is conjugated to the C-terminus of the gp41-binding peptide (P₁) and to the C-terminus of the Fc domain monomer (B).

24. The fusion protein of any one of claims 16, 17, 22, or 23, wherein L₂ comprises a chemical linker that is covalently conjugated to each of B and P₂, and L₁ comprises a chemical linker that is covalently conjugated to each of B and P₁.

25. The fusion protein of any one of claims 16, 17, 22, or 23, wherein P₂, B, and P₁ are expressed as separate polypeptide chains, P₂ and B are subsequently each covalently conjugated to L₂, and P₁ and B are subsequently each covalently conjugated to L₁.

26. The fusion protein of any one of claims 1-25, wherein P₁ and P₂ are each an independently selected gp41-binding peptide comprising an amino acid sequence having at least 85% sequence identity to an amino acid selected from any one of SEQ ID NOs: 75-85.

27. The fusion protein of claim 26, wherein P₁ and P₂ are each an independently selected gp41- binding peptide comprising an amino acid sequence selected from any one of SEQ ID NOs: 75-85.

28. The fusion protein of any one of claims 1-27, wherein B is an Fc domain monomer comprising an amino acid sequence that shares at least 85% sequence identity with an amino acid sequence selected from any one of SEQ ID NOs.1-77 and 133-193.

29. The fusion protein of claim 28, wherein B is an Fc domain monomer comprising an amino acid sequence selected from any one of SEQ ID NOs.1-77 and 133-193.

30. The fusion protein of claim 4, wherein the fusion protein is a fusion protein of Table 1 or Table 2.

31. The fusion protein of claim 4 or 30, wherein the fusion protein comprises an amino acid sequence that shares at least 85% sequence identity with an amino acid sequence selected from any one of SEQ ID NOs: 129-132 and 194-207.

32. The fusion protein of claim 31, wherein the fusion protein comprises the amino acid of any one of SEQ ID NOs: 129-132 and 194-207.

33. A conjugate comprising a first fusion protein described by any one of claims 1-32; and a second fusion protein described by any one of claims 1-32; wherein the Fc domain monomer (B) of the first fusion protein and the Fc domain monomer (B) of the second fusion protein dimerize to form an Fc domain.

34. The conjugate of claim 33, wherein the first fusion protein and the second fusion protein have the same structure and the conjugate is a homodimer.

35. A pharmaceutical composition comprising a fusion protein of any one of claims 1-32, or a conjugate of any one of claims 33 or 34, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

36. A method for treating a subject having a viral infection or presumed to have a viral infection, the method comprising administering to the subject an effective amount of a fusion protein of any one of claims 1-32, or a conjugate of any of claims 33 or 34, or a composition of claim 35.

37. A method for the prophylactic treatment of a viral infection in a subject in need thereof, the method comprising administering to the subject an effective amount of a fusion protein of any one of claims 1-32, a conjugate of any of claims 33 or 34, or a composition of claim 35.

38. The method of claim 36 or 37, wherein the viral infection is caused by human immunodeficiency virus (HIV).

39. The method of claim 38, wherein the HIV is HIV-1 or HIV-2.

40. The method of any one of claims 36-39, wherein the subject is immunocompromised.

41. The method of any one of claims 36-40, wherein the subject has been diagnosed with humoral immune deficiency, T cell deficiency, neutropenia, asplenia, or complement deficiency.

42. The method of any one of claims 36-41, wherein the subject is being treated or is about to be treated with an immunosuppressive therapy.

43. The method of any one of claims 36-41, wherein said subject has been diagnosed with a disease which causes immunosuppression.

44. The method of claim 43, wherein the disease is cancer.

45. The method of claim 44, wherein the cancer is leukemia, lymphoma, or multiple myeloma.

46. The method of any one of claims 36-45, wherein the subject has undergone or is about to undergo hematopoietic stem cell transplantation.

47. The method of any one of claims 36-46, wherein the subject has undergone or is about to undergo an organ transplant.

48. The method of any one of claims 36-47, wherein the fusion protein, conjugate, or composition is administered intramuscularly, intravenously, intradermally, intraarterially, intraperitoneally, intralesionally, intracranially, intraarticularly, intraprostatically, intrapleurally, intratracheally, intranasally, intravitreally, intravaginally, intrarectally, topically, intratumorally, peritoneally, subcutaneously, subconjunctival, intravesicularlly, mucosally, intrapericardially, intraumbilically, intraocularally, orally, locally, by inhalation, by injection, or by infusion.

49. The method of any one of claims 36-48, wherein the subject is treated with a second therapeutic agent.

50. The method of claim 49, wherein the second therapeutic agent is an antiviral agent.

51. The method of claim 50, wherein the antiviral agent is selected from an integrase inhibitor, a nucleoside reverse transcriptase inhibitor (NRTI), a non-nucleoside reverse transcriptase inhibitor (NNRTI), a protease inhibitor, an inhibitor of viral entry, a CCR5 antagonist, or a CYP3A inhibitor.

52. The method of claim 51, wherein the integrase inhibitor is selected from dolutegravir, elvitegravir, or raltegravir.

53. The method of claim 51, wherein the NRTI is selected from abacavir, lamivudine, zidovudine, emtricitabine, tenofovir, emtricitabine, didanosine, or stavudine.

54. The method of claim 51, wherein the NNRTI is selected from efavirenz, etravirine, nevirapine, rilpivirine, or delavirdine.

55. The method of claim 51, wherein the protease inhibitor is selected from atazanavir, cobicistat, darunavir, cobicistat, lopinavir, ritonavir, fosamprenavir, tipranavir, nelfinavir, indinavir, or saquinavir.

56. The method of claim 51, wherein the inhibitor of viral entry is enfuvirtide.

57. The method of claim 51, wherein the CCR5 antagonist is maraviroc.

58. The method of claim 51, wherein the CYP3A inhibitor is cobicistat or ritonavir.