Long lasting fusion peptide inhibitors of viral infection
View Patent ↗Peptides exhibiting anti-viral and anti-fusogenic activity are modified to provide greater stability and improved half-life in vivo. The selected peptides include fusion inhibitors DP178 and DP107 and related peptides and analogs thereof. The modified peptides are capable of forming covalent bonds with one or more blood components, preferably a mobile blood component.
1. An anti-viral peptide-albumin conjugate comprising
an anti-viral peptide comprising a maleimide containing group and an amino acid sequence wherein said sequence is selected from the group consisting of SEQ ID NO:2, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, SEQ ID NO:542, SEQ ID NO:543, SEQ ID NO:544, and SEQ ID NO: 545, wherein said sequence exhibits an anti-viral activity against human immunodeficiency virus (HIV) and said peptide is covalently bonded to cysteine 34 of albumin through said maleimide containing group to form said peptide-albumin conjugate, wherein the ratio of peptide to albumin in said conjugate is 1:1.
2. The anti-viral peptide-albumin conjugate of claim 1 wherein said amino acid sequence is SEQ ID NO:2.
3. The anti-viral peptide-albumin conjugate of claim 1 wherein said amino acid sequence is selected from the group consisting of SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, SEQ ID NO:542, SEQ ID NO:543, SEQ ID NO:544, and SEQ ID NO:545.
4. A composition for use in the treatment of acquired immune deficiency syndrome (AIDS) comprising, in a physiologically acceptable medium, an anti-viral peptide-albumin conjugate comprising an anti-viral peptide comprising a maleimide containing group and an amino acid sequence wherein said sequence is selected from the group consisting of SEQ ID NO:2, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, SEQ ID NO:542, SEQ ID NO:543, SEQ ID NO:544, and SEQ ID NO:545, wherein said sequence exhibits an anti-viral activity against human immunodeficiency virus (HIV) and said peptide is covalently bonded to cysteine 34 of albumin through said maleimide containing group to form said anti-viral peptide-albumin conjugate, wherein the ratio of peptide to albumin in said conjugate is 1:1.
5. The composition of claim 4 wherein said amino acid sequence is SEQ ID NO:2.
6. The composition of claim 4 wherein said amino acid sequence is selected from the group consisting of SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, SEQ ID NO:542, SEQ ID NO:543, SEQ ID NO:544, and SEQ ID NO:545.
7. A composition comprising the anti-viral peptide albumin conjugate of claim 1 in a physiologically acceptable medium.
8. The composition of claim 7 wherein said amino acid sequence is SEQ ID NO:2.
9. The composition of claim 7 wherein said amino acid sequence is selected from the group consisting of SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, SEQ ID NO:542, SEQ ID NO 543, SEQ ID NO:544, and SEQ ID NO:545.
10. The anti-viral peptide-albumin conjugate of claim 1 wherein said amino acid sequence is SEQ ID NO:147.
11. The anti-viral peptide-albumin conjugate of claim 1 wherein said amino acid sequence is SEQ ID NO:148.
12. The anti-viral peptide-albumin conjugate of claim 1 wherein said amino acid sequence is SEQ ID NO:149.
13. The anti-viral peptide-albumin conjugate of claim 1 wherein said amino acid sequence is SEQ ID NO:179.
14. The anti-viral peptide-albumin conjugate of claim 1 wherein said amino acid sequence is SEQ ID NO:180.
15. The anti-viral peptide-albumin conjugate of claim 1 wherein said amino acid sequence is SEQ ID NO:181.
16. The anti-viral peptide-albumin conjugate of claim 1 wherein said amino acid sequence is SEQ ID NO:542.
17. The anti-viral peptide-albumin conjugate of claim 1 wherein said amino acid sequence is SEQ ID NO:543.
18. The anti-viral peptide-albumin conjugate of claim 1 wherein said amino acid sequence is SEQ ID NO:544.
19. The anti-viral peptide-albumin conjugate of claim 1 wherein said amino acid sequence is SEQ ID NO:545.
20. The composition of claim 4 wherein said amino acid sequence is SEQ ID NO:147.
21. The composition of claim 4 wherein said amino acid sequence is SEQ ID NO:148.
22. The composition of claim 4 wherein said amino acid sequence is SEQ ID NO:149.
23. The composition of claim 4 wherein said amino acid sequence is SEQ ID NO:179.
24. The composition of claim 4 wherein said amino acid sequence is SEQ ID NO:180.
25. The composition of claim 4 wherein said amino acid sequence is SEQ ID NO:181.
26. The composition of claim 4 wherein said amino acid sequence is SEQ ID NO:542.
27. The composition of claim 4 wherein said amino acid sequence is SEQ ID NO:543.
28. The composition of claim 6 wherein said amino acid sequence is SEQ ID NO:544.
29. The composition of claim 4 wherein said amino acid sequence is SEQ ID NO:545.