Human immunodeficiency virus type 1 protease (HIV-1 PR)

Human immunodeficiency virus type 1 (HIV-1) protease is a homodimeric aspartic protease essential for the replication and infectivity of the virus. It functions by cleaving the nascent Gag and Gag-Pol polyproteins into functional structural proteins (matrix, capsid, and nucleocapsid) and essential enzymes (reverse transcriptase, integrase, and the protease itself). This proteolytic processing occurs during or shortly after the virus buds from the host cell, transforming immature, non-infectious particles into mature, infectious virions. As a critical therapeutic target, HIV-1 protease is inhibited by a class of drugs known as protease inhibitors (PIs), such as atazanavir. These inhibitors bind to the enzyme's active site, preventing the maturation of the virus and effectively reducing the viral load in infected individuals. However, the high mutation rate of HIV-1 often leads to the emergence of drug-resistant variants, and long-term therapy is frequently associated with metabolic complications like hyperlipidemia and insulin resistance.

Other names

HIV-1 retropepsinHIV-1 aspartic proteasePRRetropepsin

Competitive inhibition of the enzyme's active site by mimicking the transition state of the peptide substrate, thereby preventing the cleavage of viral polyproteins.