Evolving Mutational Buildup in HIV-1 Protease Shifts Conformational Dynamics to Gain Drug Resistance.

ABSTRACT: Drug resistance in antiviral treatments is a serious public health problem. Viral proteins mutate very fast, giving them a way to escape drugs by lowering drug binding affinity but with compromised function. Human immunodeficiency virus type I (HIV-1) protease, a critical antiretroviral therapeutic target, represents a model for such viral regulation under inhibition. Drug inhibitors of HIV-1 protease lose effectiveness as the protein evolves through several variants to become more resistant. However, the detailed mechanism of drug resistance in HIV-1 protease is still unclear. Here, we test the hypothesis that mutations throughout the protease alter the protein conformational ensemble to weaken protein-inhibitor binding, resulting in an inefficient protease but still viable virus. Compari

SUBMITTER: Souffrant M 

PROVIDER: S-EPMC10302472 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature