Peptides and methods of use as therapeutics and screening agents
Host RNA/viral protein interaction as a target of intervention in the replication of viruses, e.g., the human immunodeficiency virus (HIV) are described. The target being upstream of the final replication product, and being crucial to the viral replication, is less likely to be genetically altered to drug resistance. Peptides that intervene in this RNA/viral protein interaction are also described, as well as compositions containing the same and methods of use thereof.
1. A peptide comprising one or more amino acid sequences selected from:
(a) RVTHHAFLGAHRTVG (SEQ ID NO: 5);
(b) a fragment of 10 or more contiguous amino acids from an amino acid sequence of SEQ ID NO: 5;
(c) an amino acid sequence that is at least about 90% homologous to an amino acid sequence of SEQ ID: 5; or
(d) a fusion protein comprising a peptide of (a) to (c) above;
wherein the peptide is capable of interfering with the ability of a virus to use host tRNA LYS3 to prime reverse transcription.
2. The peptide of claim 1 , wherein said homologous amino acid sequence is at least about 95% homologous to an amino acid sequence of SEQ ID NO: 5.
3. The peptide of claim 1 , wherein said peptide contains a D-amino acid.
4. A therapeutic composition comprising the peptide or fusion protein of claim 1 and a pharmaceutically acceptable carrier, diluent or excipient.
5. The peptide of claim 1 , wherein said peptide prevents the viral protein from binding to an anticodon stem loop domain of the tRNA LYS3 .
6. A method of treating a lentivirus infection in a subject in need thereof, comprising administering said subject a peptide of claim 1 in a treatment effective amount.
7. The method of claim 6 , wherein said infection is a human immunodeficiency virus (HIV) infection.
8. A method of screening for a compound for treatment of a lentivirus infection, comprising:
contacting a tRNA LYS3 with at least one peptide that interacts with tRNA LYS3 ;
contacting said tRNA LYS3 and said at least one peptide with one or more candidate compounds; and
identifying the one or more candidate compounds that inhibit the interaction of tRNA LYS3 with the at least one peptide, said at least one peptide selected from:
(a) RVTHHAFLGAHRTVG (SEQ ID NO:5);
(b) a fragment of 10 or more contiguous amino acids from an amino acid sequence of SEQ ID NO:5;
(c) an amino acid sequence that is at least about 90% homologous to an amino acid sequence of SEQ ID NO:5; or
(d) a fusion protein comprising a peptide of (a) to (c) above.
9. The method of claim 8 , wherein the tRNA LYS3 is an anticodon stem loop domain of tRNA LYS3 .
10. The method of claim 9 wherein said anticodon stem loop domain of tRNA LYS3 contains one or more modified nucleoside bases.