PA-457 is an inhibitor of HIV-1 virion maturation.1,2 It inhibits the cleavage of the Gag capsid (CA) precursor CA-SP1 to the mature CA protein. PA-457 inhibits the replication of drug-sensitive and -resistant clinical isolates of HIV-1 in isolated human peripheral blood mononuclear cells (PBMCs; mean IC50s = 10.3 and 7.8 nM, respectively).3 In vivo, it prevents replication of HIV-1 in SCID-hu Thy/Liv mice when administered at a dose of 100 mg/kg.4
1.Martin, D.E., Salzwedel, K., and Allaway, G.P.Bevirimat: A novel maturation inhibitor for the treatment of HIV-1 infectionAntivir. Chem. Chemother.19(3)107-113(2008) 2.Wang, D., Lu, W., and Li, F.Pharmacological intervention of HIV-1 maturationActa Phatm. Sin. B5(6)493-499(2015) 3.Li, F., Goila-Gaur, R., Salzwedel, K., et al.PA-457: A potent HIV inhibitor that disrupts core condensation by targeting a late step in Gag processingProc. Natl. Acad. Sci. USA100(23)13555-13560(2003) 4.Soddart, C.A., Joshi, P., Sloan, B., et al.Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv micePLoS One2(11)e1251(2007)