Structural studies of antiviral inhibitor with HIV-1 protease bearing drug resistant substitutions of V32I, I47V and V82I.

ABSTRACT: HIV-1 protease inhibitors are effective in HIV/AIDS therapy, although drug resistance is a severe problem. This study examines the effects of four investigational inhibitors against HIV-1 protease with drug resistant mutations of V32I, I47V and V82I (PR_Tri) that model the inhibitor-binding site of HIV-2 protease. These inhibitors contain diverse chemical modifications on the darunavir scaffold and form new interactions with wild type protease, however, the measured inhibition constants for PR_Tri mutant range from 17 to 40 nM or significantly worse than picomolar values reported for wild type enzyme. The X-ray crystal structure of PR_Tri mutant in complex with inhibitor 1 at 1.5 Å resolution shows minor changes in interactions with inhibitor compared with the

SUBMITTER: Pawar S 

PROVIDER: S-EPMC6601333 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature