[1][2] HIV-1 PR cleaves newly synthesized polyproteins (namely, Gag and Gag-Pol[3]) at nine cleavage sites to create the mature protein components of an HIV virion, the infectious form of a virus outside of the host cell.

[1] A single active site lies between the identical subunits and has the characteristic Asp-Thr-Gly (Asp25, Thr26 and Gly27) catalytic triad sequence common to aspartic proteases.

These cleaved proteins, including reverse transcriptase, integrase, and RNaseH, are encoded by the coding region components necessary for viral replication.

The resulting hydroxyl ion attacks the carbonyl carbon of the peptide bond, forming an intermediate with a transient oxyanion, which is stabilized by the initially protonated Asp25.

HIV protease inhibitors work by specifically binding to the active site by mimicking the tetrahedral intermediate of its substrate and essentially becoming “stuck,” disabling the enzyme.

[19] There are ten HIV-1 PR inhibitors that are currently approved by the Food and Drug Administration: indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, amprenavir, fosamprenevir, atazanavir, tipranavir, and darunavir.

Secondary mutations refer to molecular changes on the periphery of the enzyme due to prolonged exposure of similar chemicals, potentially affecting inhibitor specificity for HIV-1 PR.

Other drug therapy targets include reverse transcriptase, virus attachment, membrane fusion, cDNA integration and virion assembly.