HIV Protease

Human immunodeficiency virus (HIV) protease inhibitors block the viral enzyme that cleaves Gag and Gag-Pol polyproteins. Polyprotein cleavage is needed for the maturation of new virions. In 1988 an active HIV protease was shown to be required for viral infectivity. The three-dimensional structure solved in 1989 revealed a homodimeric aspartyl protease with one catalytic aspartate from each subunit. Saquinavir, ritonavir, lopinavir, atazanavir and nelfinavir are active-site inhibitors of the HIV-1 enzyme. Ritonavir also inhibits cytochrome P450 3A4 (CYP3A4) and is used in drug metabolism studies. The list also holds HIV-1 inhibitors with other mechanisms, such as the maturation inhibitor bevirimat and the attachment inhibitor fostemsavir.