GS-8374, a Prototype Phosphonate-Containing Inhibitor of HIV-1 Protease, Effectively Inhibits Protease Mutants with Amino Acid Insertions

作者：Saskova Klara Grantz; Kozisek Milan; Stray Kirsten; de Jong Dorien; Rezacova Pavlina; Brynda Jiri; van Maarseveen Noortje M; Nijhuis Monique; Cihlar Tomas; Konvalinka Jan^*

来源：Journal of Virology, 2014, 88(6): 3586-3590.

DOI：10.1128/JVI.02688-13

Insertions in the protease (PR) region of human immunodeficiency virus (HIV) represent an interesting mechanism of antiviral resistance against HIV PR inhibitors (Pis). Here, we demonstrate the improved ability of a phosphonate-containing experimental HIV PI, GS-8374, relative to that of other PIs, to effectively inhibit patient-derived recombinant HIV strains bearing PR insertions and numerous other mutations. We correlate enzyme inhibition with the catalytic activities of corresponding recombinant PRs in vitro and provide a biochemical and structural analysis of the PR-inhibitor complex.

• 出版日期2014-3