Human immunodeficiency virus 2 protease (HIV-2 PR)

Human immunodeficiency virus 2 protease is a viral aspartic protease enzyme essential for the HIV-2 life cycle. It functions as a homodimer of 99 amino acid residues per monomer, assembling into a structure with an active site at the dimer interface containing a conserved Asp-Thr-Gly catalytic motif[1][3]. This protease cleaves the viral Gag and Gag-Pol precursor polyproteins at specific sites, a process required for maturation of viral particles and thus infectivity[1][4][5]. Structurally, HIV-2 protease is highly similar to HIV-1 protease, but differs in certain residues near the active site that affect inhibitor binding and drug susceptibility[2][3]. Several protease inhibitors (notably darunavir, saquinavir, lopinavir) can inhibit HIV-2 protease, though efficacy is reduced for most FDA-approved drugs compared to HIV-1, largely due to natural sequence differences and drug-resistance mutations[1][2]. Inhibition of HIV-2 protease is a clinically validated antiviral strategy in HIV/AIDS therapy, making it a prototypical drug target for antiretroviral drug development[4].

Other names

HIV-2 PRHIV-2 aspartic proteaseHIV type 2 protease

Protease inhibitors competitively bind to the active site of HIV-2 protease, preventing cleavage of Gag and Gag-Pol polyproteins, thus blocking maturation of the virus and production of infectious particles[4][6][2].