Blockade of sars-cov-2 infection using hydrocarbon stapled peptides

Patent metadata

Field	Value
Publication number	US-2024052330-A1
Application number	US-202118257257-A
Country	US
Kind code	A1
Filing date	Dec 22, 2021
Priority date	Dec 22, 2020
Publication date	Feb 15, 2024
Grant date	—

Abstract

The disclosure is directed to methods of inhibiting coronavirus infection using a hydrocarbon stapled peptide which is a peptidomimetic of the human angiotensin-converting enzyme 2 (hACE2). The hydrocarbon stapled peptide binds to the receptor binding domain (RBD) of a coronavirus spike protein (S) and inhibits binding of the coronavirus to hACE2 expressed on the surface of host cells.

First claim

1 . A method of inhibiting binding of a coronavirus to a human angiotensin-converting enzyme 2 (hACE2) expressed on the surface of a cell, which comprises contacting one or more cells expressing hACE2 with a hydrocarbon stapled peptide, whereby the hydrocarbon stapled peptide binds to the receptor binding domain (RBD) of a coronavirus spike protein (S) and inhibits binding of the coronavirus to hACE2.

2 . The method of claim 1 , wherein the coronavirus is coronavirus OC43, coronavirus 229E, coronavirus NL63, coronavirus HKU1, MERS-CoV, SARS-CoV, or SARS-CoV-2.

3 . The method of claim 1 or claim 2 , wherein the coronavirus is SARS-CoV-2.

4 . The method of any one of claims 1 - 3 , wherein the hydrocarbon stapled peptide is a hACE2 peptidomimetic.

5 . The method of any one of claims 1 - 4 , wherein the hydrocarbon stapled peptide mimics the alpha-helical domain of hACE2.

6 . The method of any one of claims 1 - 5 , wherein the hydrocarbon stapled peptide is single- or double-stapled.

7 . The method of any one of claims 1 - 6 , wherein the hydrocarbon stapled peptide comprises at least 70% sequence identity with an amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO:
7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, or SEQ ID NO: 25.

8 . The method of claim 7 , wherein the hydrocarbon stapled peptide comprises an amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, or SEQ ID NO: 25.

9 . The method of any one of claims 1 - 8 , wherein the hydrocarbon stapled peptide is encapsulated in a polymersome.

10 . The method of any one of claims 1 - 8 , wherein the hydrocarbon stapled peptide is packaged as a peptide amphiphile or a mucoadhesive polymer.

11 . The method of any one of claims 1 - 10 , wherein the one or more cells expressing hACE2 are present in a human.

12 . The method of claim 11 , wherein contacting one or more cells expressing hACE2 with a hydrocarbon stapled peptide comprises administering the hydrocarbon stapled peptide to the human via intranasal, intravenous, or oral administration.

13 . A method of treating a coronavirus infection in a subject, which comprises administering to the subject a hydrocarbon stapled peptide, whereby the hydrocarbon stapled peptide binds to the receptor binding domain (RBD) of a coronavirus spike protein (S) and inhibits binding of the coronavirus to hACE2 expressed by cells in the subject, thereby treating the coronavirus infection in the subject.

14 . The method of claim 13 , wherein the coronavirus is coronavirus OC43, coronavirus 229E, coronavirus NL63, coronavirus HKU1, MERS-CoV, SARS-CoV, or SARS-CoV-2.

15 . The method of claim 13 or claim 14 , wherein the coronavirus is SARS-CoV-2.

16 . The method of any one of claims 13 - 15 , wherein the hydrocarbon stapled peptide is a hACE2 peptidomimetic.

17 . The method of any one of claims 13 - 16 wherein the hydrocarbon stapled peptide mimics the alpha-helical domain of hACE2.

18 . The method of any one of claims 13 - 1617 wherein the hydrocarbon stapled peptide is single- or double-stapled.

19 . The method of any one of claims 13 - 18 , wherein the hydrocarbon stapled peptide comprises at least 70% sequence identity with an amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, or SEQ ID NO: 25.

20 . The method of claim 19 , wherein the hydrocarbon stapled peptide comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, or SEQ ID NO: 25.

21 . The method of any one of claims 13 - 20 , wherein the hydrocarbon stapled peptide is encapsulated in a polymersome.

22 . The method of any one of claims 13 - 20 , wherein the hydrocarbon stapled peptide is packaged as a peptide amphiphile or a mucoadhesive polymer.

23 . The method of any one of claims 13 - 22 , wherein the hydrocarbon stapled peptide is delivered to the human via intranasal, intravenous, or oral administration.

24 . Use of a hydrocarbon stapled peptide for the treatment of a coronavirus infection in a subject.

25 . A composition comprising a hydrocarbon stapled peptide and a pharmaceutically acceptable carrier, wherein the hydrocarbon stapled peptide comprises at least 70% sequence identity with an amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, or SEQ ID NO: 25.

26 . A composition comprising a hydrocarbon stapled peptide and a pharmaceutically acceptable carrier, wherein the hydrocarbon stapled peptide comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, or SEQ ID NO: 25.

27 . The composition of claim 25 or 26 , which is in the form of a polymersome, a peptide amphiphile, or a mucoadhesive polymer.

Assignees

• Univ Chicago

Inventors

• Tian Yu
• Jiang Sicheng
• Hubbell Jeffrey A
• Tirrell Matthew A
• Labelle James L

Classifications

• C07K16/104

  Severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2] · CPC title

• A61P31/14 Primary

  for RNA viruses · CPC title

• C12N9/485 Primary

  Exopeptidases (3.4.11-3.4.19) · CPC title

• A61K38/4813

  Exopeptidases (3.4.11. to 3.4.19) · CPC title

• C12Y304/17023

  Angiotensin-converting enzyme 2 (3.4.17.23) · CPC title