Polypeptides directed against viral infection and uses thereof
According to embodiments, at least one polypeptide comprising at least one antiviral single domain antibody and their methods of use in antiviral treatment are provided. More specifically, embodiments provide at least one polypeptide having at least one anti-viral single domain antibody (e.g. anti-Hepatitis B Virus) for targeting a guanine-rich region of the viral DNA, inhibiting transcription of the viral DNA.
1. At least one polypeptide comprising at least one antiviral single domain antibody for targeting a guanine-rich region of viral DNA, wherein the at least one antiviral single domain antibody comprises an anti-Hepatitis B Virus (HBV)single domain antibody comprising amino acid sequence selected from the group consisting of SEQ ID NOs: 9, 10, 11, 12, 13, 14, 15, 16 and 17.
2. The polypeptide in claim 1 , wherein the guanine-rich region of the viral DNA comprises a guanine-rich region of viral covalently closed circular DNA (cccDNA).
3. The polypeptide of claim 2 , wherein the guanine-rich region of the cccDNA forms a guanine-quadruplex and the at least one single domain antibody binds the guanine-quadruplex.
4. The polypeptide of claim 1 , wherein the polypeptide comprises at least one modification to include at least one coding sequence that binds at least one hepatocyte cell surface receptor.
5. The polypeptide of claim 4 , wherein the at least one at least one coding sequence may comprise a sodium taurocolate cotransporting polypeptide sequence from HBV preS1 protein.
6. The polypeptide of claim 5 , wherein the at least one coding sequence is SEQ ID NO: 4 or SEQ ID NO: 5.
7. The polypeptide of claim 1 , wherein the polypeptide comprises at least one modification to include at least one coding sequence that binds a cell penetrating peptide.
8. The polypeptide of claim 7 , wherein the cell penetrating peptide coding sequence is SEQ ID NO: 3.
9. The polypeptide of claim 1 , wherein the polypeptide comprises at least one modification to include at least one coding sequence for cell nuclear localization.
10. The polypeptide of claim 9 , wherein the at least one nuclear localization coding sequence is SEQ ID NO: 6.
11. The polypeptide of claim 1 , wherein the at least one polypeptide further comprises at least one linker, wherein the linker is SEQ ID NO: 7.
12. The polypeptide of claim 1 , wherein the at least one polypeptide further comprises at least one thrombin cleavage site, wherein the at least one thrombin cleavage site is SEQ ID NO: 8.
13. A pharmaceutical composition for treating a viral infection, the composition comprising at least one polypeptide comprising at least one antiviral single domain antibody for targeting a guanine-rich region of viral DNA and a carrier, wherein the at least one antiviral single domain antibody comprises an anti-HBV single domain antibody comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 9, 10, 11, 12, 13, 14, 15, 16 and 17.
14. The pharmaceutical composition of claim 13 , wherein the guanine-rich region of the viral cccDNA comprises a guanine-rich region of viral covalently closed circular DNA (cccDNA).
15. The pharmaceutical composition of claim 14 wherein the guanine-rich region of the viral cccDNA forms a guanine-quadruplex and the single domain antibody binds the guanine-quadruplex.
16. The pharmaceutical composition of claim 13 , wherein the at least one polypeptide comprises at least one modification selected from the group consisting of at least one coding sequence that binds at least one cell surface receptor, at least one coding sequence that binds a cell penetrating peptide, and at least one coding sequence for cell nuclear localization.
17. The pharmaceutical composition of claim 16 , wherein the at least one coding sequences are selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 3, and SEQ ID NO: 6.
18. The pharmaceutical composition of claim 13 , wherein the at least one polypeptide comprises a modification selected from at least one linker consisting of SEQ-ID SEQ ID NO: 7 and at least one thrombin cleavage site consisting of SEQ ID NO: 8.
19. The pharmaceutical composition of claim 13 , wherein a pharmaceutically effective amount of the composition is administered to a subject.
20. A method for treating a viral infection, the method comprising administering a pharmaceutically effective amount of at least one polypeptide comprising at least one antiviral single domain antibody for targeting a guanine-rich region of viral DNA to a subject, wherein the at least one antiviral single domain antibody comprises an anti-HBV single domain antibody comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 9, 10, 11, 12, 13, 14, 15, 16 and 17.
21. The method of claim 20 , wherein the guanine-rich region of the viral DNA comprises a guanine-rich region of viral covalently closed circular DNA (cccDNA).
22. The method of claim 21 , wherein the guanine-rich region of the viral cccDNA forms a guanine-quadruplex and the single domain antibody binds the guanine-quadruplex to inhibit transcription of the cccDNA.
23. The method of claim 20 , wherein the at least one polypeptide comprises at least one modification selected from the group consisting of at least one coding sequence that binds at least one cell surface receptor, at least one coding sequence that binds a cell penetrating peptide, and at least one coding sequence for cell nuclear localization.
24. The method of claim 23 , wherein the at least coding sequences are selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 3, and SEQ ID NO: 6.
25. The method of claim 20 , wherein the at least one polypeptide comprises a modification selected from at least one linker consisting of SEQ ID NO: 7 and at least one thrombin cleavage site consisting of SEQ ID NO: 8.