Molecular dynamics study on the effect of the N1 neuraminidase double mutant G147R/H274Y on oseltamivir sensitivity.

ABSTRACT: Inhibition of neuraminidase is the most prominent target in influenza medication using oseltamivir as an inhibitor. However, the emerging resistance of neuraminidase toward oseltamivir due to mutation reduces the efficacy of oseltamivir. The generally reported mutation is a single mutation at H274Y, which declines the sensitivity of oseltamivir by almost 900 folds compared to the wild-type variant. Moreover, an additional mutation at G147R increases the resistance by more than 2000 folds. However, sufficient studies on the resistance mechanism of this variant have not yet been reported. Therefore, we simulated four neuraminidase proteins comprising wild-type (WT), G147R, H274Y, and G147R/H274Y using molecular dynamics simulation to disclose the binding mechanism of oseltamivir. Trajectory

SUBMITTER: Nurrohman AI 

PROVIDER: S-EPMC11629752 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature