A group of scientists at Scripps Research Institute has identified two compounds that bind to the HIV protease in novel locations, a discovery that opens the door to a new class of treatments that can either improve existing drugs, combat resistant strains or counter any growing resistance to currently used therapies.
"The study's results open the door to a whole new approach to drug design against HIV protease," says Scripps Research Associate Professor C. David Stout, the senior author of the study. "The fragments bound at not one, but two, different crevices in protease outside the active site. This is an important proof-of-concept that the protease molecule has two non-active site binding pockets ('allosteric sites') which can now be exploited as a powerful new strategy to combat drug-resistance in HIV."
"The experiments validate my hypothesis developed from computational modeling that HIV protease has pockets on its surface besides the active site that can bind drugs," says Research Associate Alex Perryman. "Drugs developed to target these sites could be used to make current FDA-approved active site inhibitors more potent and to restore their effectiveness against drug-resistant superbugs. The whole strategy of targeting non-active sites may also prove useful against other diseases, especially when there are mutations that cause drug resistance."
The research will appear as the cover story of the March issue of the journal Chemical Biology & Drug Design.
- here's the story on the discovery