Molecular biophysics and inhibition mechanism of influenza virus A M2 viroporin by adamantane-based drugs - Challenges in designing antiviral agents.

ABSTRACT: The influenza A matrix 2 (AM2) protein is a prototype viroporin that conducts protons through an array of water molecules and sidechains of ionizable amino acid residues, with His37 being the most important. Amantadine is a prototype AM2 channel blocker and inhibitor of influenza A AM2 wild type (serine-31) replication. Amantadine received approval for prophylaxis against the influenza virus A in 1966. However, the characterization of the mechanism of action of amantadine targeting AM2 came 50 years after its approval as an anti-influenza A drug. We present results from experimental biophysical methods and molecular dynamics simulations for the complexes of the AM2 WT and amantadine-resistant mutant channels (V27A, L26F, S31N) in complex with adamantane-based ligands. Additionally, we desc

SUBMITTER: Georgiou K 

PROVIDER: S-EPMC11889636 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature