Flavivirus-Binding, Entry-Obstructing, Protease-Resistant Peptide (RI57)

• US 20180155398A1
• Filed: 12/06/2016
• Published: 06/07/2018
• Est. Priority Date: 12/06/2016
• Status: Active Grant

• Current Assignee: Ennaid Therapeutics, LLC
• Original Assignee: Ennaid Therapeutics, LLC
• Inventors: Michael, Scott F., Isern, Sharon
• Granted Patent: US 10,639,380 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 47/643 Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
• CPC Class Codes: C07K 14/001 by chemical synthesis
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention pertains to inhibitors bindable to regions of a virus. More particularly, the invention relates to inhibitors bindable to regions of flaviviral envelope glycoprotein, or flaviviral virus E protein, a class II viral E protein. Even more particularly, the invention relates to peptides inhibitory to virus-to-cell fusion and virus entry into animal cells. The invention also contains methods of determining said inhibitors, bindable to regions of the flaviviral E protein complex, (e.g., those of dengue and zika viruses) as candidates for in vivo anti-viral compounds that are also resistant to degradation by peptidases and thus extraordinarily suitable for oral, in addition to other, routes of administration.

Claims

1. A protease-resistant flavivirus-targeted cell entry-inhibitory peptide consisting of 28 amino acids arranged in an enantiopure, D-amino acid sequence presented as SEQ ID NO:

1.

2. The cell entry-inhibitory peptide of claim 1, wherein the cell entry-inhibitory peptide blocks a flaviviral class II envelope protein.

3. The cell entry-inhibitory peptide of claim 2, wherein the class II envelope protein is a flaviviral E protein.

4. The cell entry-inhibitory peptide of claim 3, wherein the cell entry-inhibitory peptide inhibits flavivirus virion-to-cell (animal) fusion.

5. The peptide of claim 4, wherein the flavivirus is dengue virus.

6. The peptide of claim 4, wherein the flavivirus is Zika virus.

7. A pharmaceutical composition comprising the cell entry-inhibitory peptide of claim 1 and a biocompatible carrier.

8. The pharmaceutical composition of claim 7, wherein at least one of the amino acids comprising the cell entry-inhibitory peptide is substituted with a functionally equivalent amino acid.

9. The pharmaceutical composition of claim 7, wherein the peptide contains up to 20 percent additional amino acid residues.

10. The pharmaceutical composition of claim 8, wherein the at least one functionally equivalent amino acid is selected from the group consisting of benzylated derivatives, glycosylated derivatives, and peptide enantiomers of naturally-occurring amino acids.

11. The pharmaceutical composition of claim 7, wherein the biocompatible carrier is selected from the group consisting of saline, buffered saline, dextrose, surfactant/spreading agent, and water.

12. A method of treatment of flaviviral infections in human patients comprising selecting a route of administration and administering a therapeutically effective amount of a peptide having an amino acid sequence presented as SEQ ID NO:

1 to said patients.

13. The method of claim 12, wherein the peptide inhibits flaviviral virion-to-cell fusion.

14. The method of claim 12, wherein the route of administration is selected from the group consisting of oral, intranasal, aerosol inhalation, intradermal, intramuscular, intraperitoneal, intrarectal, intravenous, subcutaneous, and injection into spinal fluid.

15. The method of claim 12, wherein the peptide administered is linked to a molecular carrier.

16. The method of claim 15, wherein the molecular carrier is human serum albumin (HSA).

17. The method of claim 12, wherein the peptide is administered to an animal susceptible to said flaviviral infection.