Development of a new type of protease inhibitors, efficacious against FIV and HIV variants

Based on the structural analysis of FIV protease and drug-resistant HIV pro teases and molecular modeling, a new type of inhibitors with a small P3 res idue has been developed. These inhibitors are effective against HIV and its drug-resistant mutants, as well as SIV and FIV. Modification of existing H IV protease inhibitors by reducing the size of the P3 residue has the same effect. This finding provides a new strategy for the development of HIV pro tease inhibitors effective against the wild-type and drug-resistant mutants . It further supports the use of FIV protease as a useful model for drug-re sistant HIV proteases, which often have a more constricted binding region f or the P3 group or the combined P3 and P1 groups.