Molecular dynamics simulation directed rational design of inhibitors targeting drug-resistant mutants of influenza A virus M2.

ABSTRACT: Influenza A virus M2 (A/M2) forms a homotetrameric proton selective channel in the viral membrane. It has been the drug target of antiviral drugs such as amantadine and rimantadine. However, most of the current virulent influenza A viruses carry drug-resistant mutations alongside the drug binding site, such as S31N, V27A, and L26F, etc., each of which might be dominant in a given flu season. Among these mutations, the V27A mutation was prevalent among transmissible viruses under drug selection pressure. Until now, V27A has not been successfully targeted by small molecule inhibitors, despite years of extensive medicinal chemistry research efforts and high throughput screening. Guided by molecular dynamics (MD) simulation of drug binding and the influence of drug binding on the dynamics of A

SUBMITTER: Wang J 

PROVIDER: S-EPMC3354620 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature