Important note: Information in this article was accurate in 2007. The state of the art may have changed since the publication date.
Los Angeles Times - April 21, 2007
Thomas H. Maugh II, thomas.maugh@latimes.com
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 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 has yet proved useful as a therapeutic or preventive agent. The team does not yet 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 the 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. They have so far 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 the strains of HIV the researchers tested, and none of those strains appeared to develop resistance to its activity. 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 conducted with researchers at IPF Pharmaceuticals in Hannover show that the synthetic peptide is safe in animals at even high concentrations.
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