Methods and compositions related to inhibition of viral entry

Patent metadata

Field	Value
Publication number	US-10512665-B2
Application number	US-201615171753-A
Country	US
Kind code	B2
Filing date	Jun 2, 2016
Priority date	Feb 8, 2007
Publication date	Dec 24, 2019
Grant date	Dec 24, 2019

Abstract

Disclosed are compositions and methods for inhibiting viral entry.

First claim

What is claimed is:

1. A method for inhibiting human immunodeficiency virus 1 (HIV1) entry into a cell, comprising exposing the HIV1 to a composition, the composition comprising at least one D-peptide that interacts with the N-trimer pocket of gp41 protein, wherein the at least one D-peptide comprises the amino acid sequence of SEQ ID NO: 36,
thereby inhibiting HIV1 entry into the cell.

2. The method of claim 1 , wherein the composition is a pharmaceutical composition comprising the at least one peptide and a pharmaceutically acceptable carrier.

3. A method of treating human immunodeficiency virus 1 (HIV1) infection in a subject comprising administering to the subject an effective amount of a pharmaceutical composition, the pharmaceutical composition comprising (a) at least one D-peptide that interacts with the N-trimer pocket of gp41 protein, wherein the at least one D-peptide comprises the amino acid sequence of SEQ ID NO: 36, and (b) a pharmaceutically acceptable carrier.

4. The method of claim 3 , wherein the pharmaceutical composition is administered in conjunction with at least one additional antiviral agent.

5. The method of claim 4 , wherein the at least one additional antiviral agent is selected from the group consisting of a viral replication inhibitor, a viral protease inhibitor, a viral reverse transcriptase inhibitor, a viral entry inhibitor, a viral integrase inhibitor, a viral Rev inhibitor, a viral Tat inhibitor, a viral Nef inhibitor, a viral Vpr inhibitor, a viral Vpu inhibitor, and a viral Vif inhibitor.

6. The method of claim 3 , wherein the at least one D-peptide is linked to at least one other D-peptide.

7. The method of claim 6 , wherein a crosslinker is used to multimerize the D-peptides.

8. The method of claim 7 , wherein the crosslinker is PEG.

9. The method of claim 6 , wherein the D-peptides are crosslinked into branched structures.

10. The method of claim 6 , wherein the N-termini of the D-peptides are crosslinked.

11. The method of claim 6 , wherein the C-termini of the D-peptides are crosslinked.

12. The method of claim 6 , wherein the N-terminus of one D-peptide and the C-terminus of the other D-peptide are crosslinked.

13. The method of claim 3 , wherein the at least one D-peptide comprises an amino acid sequence of any one of SEQ ID NOS: 3, 4, 5, 6, 7, 42, 43, 44, 12, 13, 23, 24, 25, 26, 27, 28, and 29, or a fragment thereof.

14. The method of claim 13 , wherein the at least one D-peptide comprises an amino acid sequence of SEQ ID NO: 26, or a fragment thereof.

15. The method of claim 3 , wherein the at least one D-peptide comprises an amino acid sequence as set forth in GACDYXEWXWLCAA (SEQ ID NO:42).

16. The method of claim 15 , wherein:
(a) one or two lysine residues are linked to the N-terminus of the N-terminal flanking sequence; or
(b) one or two lysine residues are linked to the C-terminus of the C-terminal flanking sequence.

17. The method of claim 13 , wherein the at least one D-peptide is capped at its N-terminus and its C-terminus.

18. The method of claim 16 , wherein the at least one D-peptide is capped at its N-terminus and its C-terminus.

19. The method of claim 17 , wherein the N-terminus is capped with an acetyl group and the C-terminus is capped with an amide group.

20. The method of claim 18 , wherein the N-terminus is capped with an acetyl group and the C-terminus is capped with an amide group.

21. The method of claim 17 , wherein at least two D-peptides comprising an amino acid sequence of SEQ ID NO:3, 4, 5, 6, 7, 43, 12, or 25, are cross-linked via an N-terminal lysine residue in each of the D-peptides.

22. The method of claim 17 , wherein at least two D-peptides comprising an amino acid sequence of SEQ ID NO:23, 24, 25, 26, 27, 28, or 29 are cross-linked via a C-terminal lysine residue in each of the D-peptides.

23. The method of claim 17 , wherein at least two D-peptides comprising an amino acid sequence of SEQ ID NO:27 are cross-linked via an internal lysine residue in each of the D-peptides.

24. The method of claim 22 , wherein at least two D-peptides comprising an amino acid sequence of SEQ ID NO:26 are crosslinked via a C-terminal lysine residue in each of the D-peptides.

25. The method of claim 22 , wherein three D-peptides comprising an amino acid sequence of SEQ ID NO:26 are crosslinked via a C-terminal lysine residue in each of the D-peptides.

Assignees

• Univ Utah Res Found

Inventors

• Kay Michael S
• Welch Brett D

Classifications

• A61P31/18

  for HIV · CPC title

• A61P31/12

  Antivirals · CPC title

• A61K47/641

  Branched, dendritic or hypercomb peptides · CPC title

• A61K47/55

  the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug · CPC title

• A61K47/60

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title