HIV-1 protease enzyme (HIV-1 PR)

HIV‑1 protease is a retroviral aspartyl protease essential for the maturation and infectivity of human immunodeficiency virus type 1 (HIV‑1), which causes AIDS. The mature enzyme is a homodimer composed of two identical subunits, each 99 amino acids long. Its primary function is to cleave newly synthesized polyprotein precursors—Gag and Gag‑Pol—at specific sites during virion assembly. This processing produces functional proteins required for assembling mature infectious virions; without it, new virus particles remain non-infectious. The active site contains two catalytic aspartate residues that mediate peptide bond hydrolysis via a water molecule. Because its activity is indispensable for viral replication but absent in human cells outside infection contexts, it has been a major therapeutic target since early in AIDS drug development. Inhibitors designed against its structure have revolutionized antiretroviral therapy by effectively suppressing viral replication when used in combination regimens.

Other names

HIV proteaseRetroviral aspartyl proteaseRetropepsinPR (abbreviation)

Drugs targeting this molecule act as protease inhibitors. They bind to the active site of the enzyme, mimicking natural substrates but resisting cleavage, thereby blocking the normal function of the enzyme and preventing maturation of infectious virus particles.