Novel mechanism for hiv-1 entry into host cells and peptides inhibiting this mechanism
OwnerFederico Bussolino, Serena Marchioinventors
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Abstract
This invention relates to the finding that TAT interacts with gp120 at the cell surface and enhances HIV-1 entry into host cells. This invention also discloses modulators of this interaction, particularly peptides that mimic the region of gp120 involved in this interaction. These peptides interfere with TAT-mediated enhancement of infection regardless of virus strain, and are therefore suitable for the development in general of broad-range drugs against AIDS and other infectious diseases induced by HIV-1 related pathogens, and specifically for a class of chemicals active in the reduction or abrogation of virus and infectivity spreading.
Claims22
Use of inhibitors of the interaction between HIV- 1 TAT protein and HIV- 1 gp 120 for inhibiting the entry of HIV-1 into a host cell.
Use of claim , wherein the pepide is selected from:
- (a) CTVECYFNCTPTC
- (SEQ ID No. 2)
- (b) CPDRKKKVVMVC
- (SEQ ID No. 3)
- (c) CSFNITTEIRDKVKK
- (SEQ ID No. 127)
- (d) a peptide comprising at least 5 contiguous amino acids from a peptide, selected from the group consisting of peptides (a)-(c),
- (e) a peptide which has a sequence identity of at least 80% to the amino acid sequence of a peptide selected from the group consisting of peptides (a)-(d).
A method for identifying and/or characterizing a compound which inhibits the entry of HIV- 1 into a host cell comprising
- (i) providing at least one compound to be tested and
- (ii) determining if the compound is capable of inhibiting the interaction between HIV-1 TAT protein and HIV-1 gp120.
A pharmaceutical composition comprising as an active ingredient at least one inhibitor of the interaction between HIV- 1 TAT protein and HIV- 1 gp120 and optionally pharmaceutically acceptable carriers, diluents and/or adjuvants.
A peptide which is selected from:
- (a) CTVECYFNCTPTC
- (SEQ ID No. 2)
- (b) CPDRKKKVVMVC
- (SEQ ID No. 3)
- (c) CSFNITTEIRDKVKK
- (SEQ ID No. 127)
- (d) a peptide comprising at least 5 contiguous amino acids from a peptide, selected from the group consisting of peptides (a)-(c),
- (e) a peptide which has a sequence identity of at least 80% to the amino acid sequence of a peptide selected from the group consisting of peptides (a)-(d).
A peptide which is selected from:
- (a) RDKKKK,
- (SEQ ID No. 40)
- (b) RDKKKQ,
- (SEQ ID No. 41)
- (c) RDKKKV,
- (SEQ ID No. 42)
- (d) RNKRKQ,
- (SEQ ID No. 51)
- (e) RDKTQK,
- (SEQ ID No. 52)
- (f) DRKKKV,
- (SEQ ID No. 43)
- (g) KDKKEK,
- (SEQ ID No. 45)
- (h) RDKQQK,
- (SEQ ID No. 49)
- (i) RDKVQK,
- (SEQ ID No. 50)
- (j) CSFNIT,
- (SEQ ID No. 4)
- (k) RDKVKK,
- (SEQ ID No. 44)
- (l) a peptide comprising at least 5 contiguous amino acids from a peptide selected from the group consisting of peptides (a)-(k),
- (m) a peptide which has an identity of at least 80 % to the amino acid sequence of peptide selected from the group consisting of peptides (a)-(l).
Peptide combination comprising at least two peptides with the sequences shown in SEQ ID NO. 2-127.
Dependencies are inferred from the claim text.