Evidence for Disruption of Mg²⁺ Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors.

ABSTRACT: HIV-1 integrase is the enzyme responsible for integrating the viral DNA into the host genome and is one of the main targets for antiretroviral therapy; however, there are documented cases of resistance against all the currently used integrase strand transfer inhibitors (INSTIs). While some resistance-related mutations occur near the inhibitor's binding site, the mutation N155H occurs on the opposite side of the drug-interacting Mg²⁺ ions, thus, not interacting directly with the drug molecules and currently lacking an explanation for its resistance mechanism. Moreover, mutation N155H and the resistance-related mutation Q148H are mutually exclusive for unknown reasons. In the present study, we use molecular dynamics simulations to understand the impact of the N155H mutation in the

SUBMITTER: Machado LA 

PROVIDER: S-EPMC7468422 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature