German researchers have found a peptide in human blood that blocks HIV and have identified a synthetic variant that is 100 times more potent, they reported Friday in the journal Cell.
The synthetic version has been shown to be safe in animals and the team hopes to begin trials in humans this year, they said.
The peptide could be a major improvement over existing anti-HIV drugs because it works equally well against drug-resistant viruses, said virologist Frank Kirchhoff of the University of Ulm, who led the team.
"That's a big advantage," he said.
Several other compounds isolated from human blood have been shown to block HIV replication, but none yet has proved useful as a therapeutic or preventive agent. The team does not know if the newly discovered compound, called "virus inhibitory peptide," or virip, plays a role in the natural resistance some people display against HIV infection.
Kirchhoff and his colleagues discovered virip by screening hundreds of thousands of proteins filtered from the blood of patients undergoing kidney dialysis.
The peptide they ultimately identified contains 20 amino acids and appears to be a fragment from the end of an enzyme called alpha-1-antitrypsin. So far, they have found no natural function for the peptide, but the extremely small quantity present in humans makes such studies difficult.
In laboratory dishes, virip blocked all strains of HIV they tested, and none of those strains appeared to develop resistance. The peptide targets a viral protein called gp41 fusion peptide, which plays a crucial role in entry of the virus into cells. That viral peptide appears to be stable to mutation, which may explain the lack of resistance to virip.
The team found that changing three amino acids in virip produced a peptide that was 100 times more potent than the naturally occurring product. Tests in animals conducted with researchers at IPF Pharmaceuticals in Hannover show that synthetic peptide is safe in animals even at high concentrations.