IP Library › Granted Patent US 12,187,767
Granted Patent B2
US 12,187,767 · App. 17/806,210 · Granted Jan 7, 2025

Compositions and methods for treating SARS-CoV-2 infections

Inventors: Vincent C. Bond (Stone Mountain, GA); Ming Bo Huang (Atlanta, GA); James W. Lillard, Jr. (Smyrna, GA)
Assignee: MOREHOUSE SCHOOL OF MEDICINE
C07K14/163A61K45/06A61K47/542A61K47/60A61P31/14A61K38/00
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Quick Facts
Patent No.
US 12,187,767
App. No.
17/806,210
Granted
Jan 7, 2025
Kind
B2
Abstract

The present application relates to methods and compositions and methods for treating viral infections, especially those caused by SARS-CoV-2. In one aspect, a method of treatment comprises administering to a subject in need of such treatment an effective amount of a pharmaceutical composition comprising a multipartite SARS-CoV-2-inhibiting peptide comprising a secretion modulating region (VI-SMR) peptide from HIV-1 Nef in combination with a cell-penetrating peptide (CPP) domain, a Clusterin (Clu)-binding peptide (Clu-BP) domain, a mitochondrial targeting (Mito-T) peptide domain, an anti-fusogenic (AF) peptide domain, a viral attachment inhibitor (VAI) domain or combination thereof, optionally where the SARS-CoV-2-inhibiting peptide is pegylated and/or modified with one or more hydrophobic domains.

Claims (17)

1. A method for treating a SARS-CoV-2 infection, comprising:

administering to a subject in need of such treatment an effective amount of a pharmaceutical composition comprising a virus-inhibiting secretion modifying region (VI-SMR) peptide comprising an SMR peptide from HIV-1 Nef in combination with a cell penetrating peptide (CPP).

2. The method of claim 1 , wherein the VI-SMR peptide comprises the amino acid sequence of VGFPVAAVGFPV (SEQ ID NO: 2), VGFPVAAVGFPVGRKKRRQRRRPPQ (SEQ ID NO: 4) or VGFPVAAVGFPVAAHPLSKHPYWSQPAAHPLSKHPYWSQP (SEQ ID NO: 48).

3. The method of claim 1 , wherein the VI-SMR peptide is administered as a single peptide further comprising an anti-SARS-CoV-2 anti-fusogenic (AF) peptide, an anti-SARS-CoV-2 viral attachment inhibitor (VAI) peptide, a mitochondrial targeting (Mito-T) peptide, Clusterin-binding peptide (Clu-BP), or combination thereof.

4. The method of claim 3 , wherein the VI-SMR peptide further comprises an AF peptide.

5. The method of claim 3 , wherein the VI-SMR peptide further comprises a VAI peptide.

6. The method of claim 3 , wherein the VI-SMR peptide further comprises a Clu-BP.

7. The method of claim 1 , wherein the VI-SMR peptide is pegylated, conjugated to a fatty acid, or both.

8. The method of claim 1 , wherein the pharmaceutical composition comprises a dimeric or multimeric VI-SMR peptide.

9. The method of claim 1 , wherein the pharmaceutical composition is administered in combination with one or more antiviral agents.

10. The method of claim 1 , wherein the VI-SMR peptide is loaded into an exosome that is administered into the subject infected with SARS-CoV-2.

11. The method of claim 1 , wherein the VI-SMR peptide is administered in combination with a mortalin inhibitor.

12. The method of claim 7 , wherein the mortalin inhibitor is omeprazole, mortaparib, or MKT-077.

13. The method of claim 1 , wherein the VI-SMR peptide is administered in combination with an AF peptide, a VAI peptide, a Clu-BP, or a combination thereof, wherein the VI-SMR peptide is administered separately from the AF peptide, VAI peptide, or Clu-BP.

14. The method of claim 3 , wherein the VI-SMR peptide is administered in combination with an AF peptide.

15. The method of claim 3 , wherein the VI-SMR peptide is administered in combination with a VAI peptide.

16. The method of claim 3 , wherein the VI-SMR peptide is administered in combination with a Clu-BP.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 7, 2022
From: BOND, VINCENT C.; HUANG, MING BO; LILLARD, JAMES W., JR.
To: MOREHOUSE SCHOOL OF MEDICINE
Reel/Frame 061342/0336 →
Continuity (3)
Continuation 17380786 · Jul 20, 2021
Division 17339197 · Jun 4, 2021
Related Publication 20220389063A1 · Dec 8, 2022
References Cited (52)
US 4569789A · Blattler et al. · 1986 [cited by applicant]
US 4631190A · Shen et al. · 1986 [cited by applicant]
US 5252714A · Harris et al. · 1993 [cited by applicant]
US 5306809A · Boon et al. · 1994 [cited by applicant]
US 5560234A · Ross et al. · 1996 [cited by applicant]
US 5665358A · Barton et al. · 1997 [cited by applicant]
US 5672662A · Harris et al. · 1997 [cited by applicant]
US 5985263A · Lee et al. · 1999 [cited by applicant]
US 5990237A · Bentley et al. · 1999 [cited by applicant]
US 8431530B2 · Bond et al. · 2013 [cited by applicant]
US 8871708B2 · Bond et al. · 2014 [cited by applicant]
US 9556224B2 · Bond · 2017 [cited by examiner]
US 10040831B2 · Bond et al. · 2018 [cited by applicant]
US 10206974B2 · Bond · 2019 [cited by examiner]
US 10544193B2 · Bond et al. · 2020 [cited by applicant]
US 10800817B2 · Bond et al. · 2020 [cited by applicant]
US 11180534B1 · Bond et al. · 2021 [cited by applicant]
US 11304991B2 · Bond · 2022 [cited by examiner]
US 20040023334A1 · Prior · 2004 [cited by applicant]
US 20040192627A1 · Weissig et al. · 2004 [cited by applicant]
US 20120121507A1 · Filfil et al. · 2012 [cited by applicant]
US 20120171115A1 · Hudson et al. · 2012 [cited by applicant]
US 20140142121A1 · Altieri et al. · 2014 [cited by applicant]
US 20140196172A1 · Eudes et al. · 2014 [cited by applicant]
US 20160237129A1 · Keefe et al. · 2016 [cited by applicant]
US 20180305412A1 · Bond et al. · 2018 [cited by applicant]
US 20190134151A1 · Bond et al. · 2019 [cited by applicant]
US 20190135873A1 · Bond et al. · 2019 [cited by applicant]
WO 2013084000 · 2013 [cited by applicant]
Riva et al. Discovery of SARS-CoV-2 Antivirals through Large-scale Drug Repositions. Nature, Oct. 2020, vol. 586, No. 7828, pp. 113-119. (Year: 2020). [cited by examiner]
Barberis et al. Circulating Exosomes Are Strongly Involved in SARS-CoV-2 Infection. Frontiers in Molecular Biosciences. Feb. 2021, vol. 3, pp. 1-18. (Year: 2021). [cited by examiner]
Guy, B. et al., “Mutational analysis of the HIV nef Protein”, Virology, 1990, vol. 176, pp. 413-425. [cited by applicant]
Campbell, T. D. et al., “HIV-1 Nef protein is secrete into vesicles that can fuse with target cells and virions”, Ethnicity & Disease, 2008, vol. 18(2), pp. S2-14-S2-19. [cited by applicant]
Sanfridson, A. et al., “Nef proteins encoded by human and simian immunodeficiency viruses induce the accumulation of endosomes and lysomes in human T cells”, Proc. Natl. Acad. Sci., 1997, vol. 94(3), pp. 873-838. [cited by applicant]
Esser M. T. et al., “Differential Incorporation of CD45, COBO (B7-1). CD88 (B7-2), and Major Histocompatibility Complex Class I and II Molecules into Human Immunodeficiency Virus Type 1 Vinions and Microvesicles: Implic… [cited by applicant]
Joliot, A. et al., “Transduction peptides: from technology to physiology”, Nature Cell Biology, 2004, vol. 6(3), pp. 189-196. [cited by applicant]
Heitz, F. et al., “Twenty years of cell-penetrating peptides: from molecular mechanisms to therapeutics”, British Journal of Pharmacology, 2009, vol. 157(2), pp. 195-206. [cited by applicant]
Gaertner, H.F. et al., “Site-specific attachment of functionalized poly(ethylene glycol) to the amino terminus of proteins”, Bioconjugate Chem., 1996, vol. 7(1), pp. 38-44. [cited by applicant]
Ali, S.A. et al., “Genetic Characterization of HIV Type 1 Nef-Induced Vesicle Secretion”, AIDS Research and Human Retroviruses, 2010, vol. 26(2), pp. 173-192. [cited by applicant]
Ellman, G. L. et al., “A new and rapid colorimetric determination of acetylcholinesterase activity”, Biochemical Pharmacology, 1961, vol. 7, pp. 88-95. [cited by applicant]
Shelton, M. N. et al., “Secretion Modification Region-Derived Peptide Disrupts HIV-1 Nef's Interaction with Mortal in and Blocks Virus and Nef Exosome Release”, Journal of Virology, 2012, vol. 86(1), pp. 406-419. [cited by applicant]
File History of U.S. Appl. No. 17/339,197, filed Jun. 4, 2021. [cited by applicant]
Riva et al. Discovery of SARS-CoV-2 antiviral drugs through large-scale comound repurposing. Nature, Oct. 2020, vol. 586, No. 7827, pp. 113-119. (Year: 2020). [cited by applicant]
Barberis et al. Circulating Exosomes Are Strongly Involved in SARS-CoV-2 Infection. Frontiers in Molecular Biosciences. Feb. 22, 2021, vol. 8, Article 632290, pp. 1-18. (Year: 2021). [cited by applicant]
Inagawa et al. Novel ACE2-IgG1 fusions with improved in vitro and in vivo activity against SARS-CoV-2, bioRxiv, Jul. 24, 2020, 21 pages. (Year: 2020). [cited by applicant]
International Search Report and Written Opinion of International Application No. PCT/US2021/040860 mailed Nov. 5, 2021. [cited by applicant]
Han et al., “Computational Design of ACE2-Based Peptide Inhibitors of SAR-CoV-2,” ACS Nano. Apr. 14, 2020 (Apr. 14, 2020), vol. 14, Issue 4, pp. 5143-5147. [cited by applicant]
Andre et l. “Exosomes as Potent Cell-Free Peptide-Based Vaccine. I. Dendritic Cell-Derived Exosomes Transfer Functional MHC Class I/Peptide Complexes to Dendritic Cells,” The Journal of Immunology. Feb. 15, 2004 (Feb. 1… [cited by applicant]
Globalda TA Heath Care. “Synthetic peptides are promising therapeutic candidates for Covid-19,” Pharmaceutical Technology. May 6, 2020 (May 26, 2020). [Oct. 7, 2021] Retrieved from internet: <URL: https ://www.pharmaceu… [cited by applicant]
Trafton. “Experimental peptide targets Covid-19: Computational modeling yields a protein fragment that could bind to coronavirus spike proteins and destroy them,” Massachusetts Institute of Technology. Jun. 22, 220 (Jun… [cited by applicant]
File History of U.S. Appl. No. 17/380,786, filed Jul. 20, 2021. [cited by applicant]
Roberts et al. Chemistry for peptide and protein PEGylation. Advanced Drug Delivery Reviews, 2002, vol. 54, pp. 459-476. (Year: 2002). [cited by applicant]