Mechanism of action of substituted peramivir phosphonate derivatives as potent oseltamivir-resistant influenza A virus using molecular docking, molecular dynamics simulations, and free energies calculations

Abstract

Abstract Peramivir, a potent influenza neuraminidase inhibitor, serves as a basis for designing similar inhibitors targeting viral, mammalian, or bacterial neuraminidases. This study employs molecular modeling, including docking, ADMET analysis, and topological approaches (ELF, RDG, AIM), to investigate the structural features essential for influenza A virus inhibition, focusing on hydrogen bonding interactions. Compounds 7 and 8 were evaluated for their potential to target oseltamivir-resistant influenza A virus binding sites. Binding affinity was assessed using AutoDock Vina, and 100 ns molecular dynamics (MD) simulations confirmed their stability. Free binding energy calculations showed that these compounds exhibit higher stability than the standard drug. The findings provide insights into the structure–activity relationship of substituted peramivir phosphonates, supporting their potential as lead compounds for early-stage drug development against influenza A infections.

Keywords

• Peramivir phosphonate
• Influenza A virus
• Molecular docking
• Free binding energy