Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance.

ABSTRACT: Protease inhibitors have the highest potency among antiviral therapies against HIV-1 infections, yet the virus can evolve resistance. Darunavir (DRV), currently the most potent Food and Drug Administration-approved protease inhibitor, retains potency against single-site mutations. However, complex combinations of mutations can confer resistance to DRV. While the interdependence between mutations within HIV-1 protease is key for inhibitor potency, the molecular mechanisms that underlie this control remain largely unknown. In this study, we investigated the interdependence between the L89V and L90M mutations and their effects on DRV binding. These two mutations have been reported to be positively correlated with one another in HIV-1 patient-derived protease isolates, with the presence of one

SUBMITTER: Henes M 

PROVIDER: S-EPMC6941756 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature