ATC Group: J05AE Protease inhibitors

Amprenavir is a competitive inhibitor of HIV-1 protease. Amprenavir binds to the active site of HIV-1 protease and thereby prevents the processing of viral gag and gag-pol polyprotein precursors, resulting in the formation of immature non-infectious viral particles.

Atazanavir is an azapeptide HIV-1 protease inhibitor (PI). The compound selectively inhibits the virus-specific processing of viral Gag-Pol proteins in HIV-1 infected cells, thus preventing formation of mature virions and infection of other cells.

Darunavir is an inhibitor of the dimerisation and of the catalytic activity of the HIV-1 protease (K_D of 4.5 × 10^-12 M). It selectively inhibits the cleavage of HIV encoded Gag-Pol polyproteins in virus infected cells, thereby preventing the formation of mature infectious virus particles.

Fosamprenavir after oral administration, is rapidly and almost completely hydrolysed to amprenavir and inorganic phosphate prior to reaching the systemic circulation. Amprenavir binds to the active site of HIV-1 protease and thereby prevents the processing of viral gag and gag-pol polyprotein precursors, resulting in the formation of immature noninfectious viral particles.

Indinavir inhibits recombinant HIV-1 and HIV-2 protease with an approximate tenfold selectivity for HIV-1 over HIV-2 proteinase. Indinavir binds reversibly to the protease active site and inhibits competitively the enzyme, thereby preventing cleavage of the viral precursor polyproteins that occurs during maturation of the newly formed viral particle.

Nelfinavir reversibly binds to the active site of HIV protease and prevents cleavage of the polyproteins resulting in the formation of immature non-infectious viral particles.

Ritonavir is an orally active peptidomimetic inhibitor of the HIV-1 and HIV-2 aspartyl proteases. Inhibition of HIV protease renders the enzyme incapable of processing the gag-pol polyprotein precursor which leads to the production of HIV particles with immature morphology that are unable to initiate new rounds of infection. Ritonavir has selective affinity for the HIV protease and has little inhibitory activity against human aspartyl proteases. Pharmacokinetic enhancement by ritonavir is based on ritonavir’s activity as a potent inhibitor of CYP3A-mediated metabolism.

Saquinavir selectively inhibits the HIV protease, thereby preventing the creation of mature infectious virus particles. The HIV protease is an essential viral enzyme required for the specific cleavage of viral gag and gag-pol polyproteins.

Tipranavir is a non-peptidic inhibitor of the HIV-1 protease that inhibits viral replication by preventing the maturation of viral particles.