The nontoxic tripeptide glycyl-prolyl-glycine amide inhibits the replication of human immunodeficiency virus type 1.
OBJECTIVE
To determine whether short peptides corresponding to the RGPGR motif of the V3 loop of gp 120 have anti-human immunodeficiency virus type 1 (anti-HIV-1) activity.


METHODS
Short peptides were tested against the HIV-1 laboratory strains and clinical isolates.


RESULTS
The tripeptide glycyl-prolyl-glycine amide (GPG-NH2) inhibited the replication of both laboratory strains and 47 clinical isolates, including 19 strains that were resistant to other drugs or that were from patients with failing therapy. The 50% inhibitory concentrations values were 2.7 to 37 microM. Phenotypic change of two isolates from nonsyncytia-inducing to syncytia-inducing did not change their sensitivity to GPG-NH2. The tripeptide added to the antiviral effect of both zidovudine and ritonavir.


CONCLUSIONS
The tripeptide GPG-NH2 is a nontoxic compound that inhibits the replication of HIV-1 by an apparently new mode of action. Glycyl-prolyl-glycine-NH2 might prove useful by itself or as a lead compound for the treatment of drug-resistant HIV-1. Glycyl-prolyl-glycine-NH2 is currently undergoing phase I/II human clinical trials in Sweden.
Su
J
J
Division of Clinical Virology, Karolinska Institutet, Stockholm, Sweden.
Andersson
E
E
Horal
P
P
Naghavi
M H
MH
Palm
A
A
Wu
Y P
YP
Eriksson
K
K
Jansson
M
M
Wigzell
H
H
Svennerholm
B
B
Vahlne
A
A
D000577:Amides / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000494:pharmacology; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D019438:Ritonavir / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*; D015215:Zidovudine / Q000494:pharmacology
D000577:Amides; D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; D017320:HIV Protease Inhibitors; C059762:HIV envelope protein gp120 (305-321); D009842:Oligopeptides; D010446:Peptide Fragments; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; C425285:glycylprolylglycine amide; D019438:Ritonavir