GS-8374, a Prototype Phosphonate-Containing Inhibitor of HIV-1 Protease,Effectively Inhibits Protease Mutants with Amino Acid Insertions |
| |
Authors: | Klára Grantz ?a?ková Milan Ko?í?ek Kirsten Stray Dorien de Jong Pavlína ?ezá?ová Ji?í Brynda Noortje M. van Maarseveen Monique Nijhuis Tomá? Cihlá? Jan Konvalinka |
| |
Abstract: | 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. |
| |
Keywords: | |
|
|