Identification of novel inhibitor phytoconstituents for Influenza A H3N2: an <i>in silico</i> approach

Abstract

Influenza A virus subtype H3N2 is a highly infectious respiratory virus that is responsible for global seasonal flu epidemics. The current study was designed to investigate the antiviral activity of 150 phytocompounds of North Western Himalayas medicinal plants by molecular docking. Two target proteins of hemagglutinin of influenza virus A (PDB ID 4WE8) and Influenza virus H3N2 nucleoprotein - R416A mutant (PDB ID 7NT8) are selected for this study. Molecular docking was done by AutoDock vina tool, toxicity and drug-likeness prediction was done by protox II and Moleinspiration. MD simulation of best protein-ligand complexes was done by using Gromacs, version 2021.5. Molecular docking and toxicity data revealed that clicoemodin and rumexocide showed the best binding with both target proteins 4WEB & 7NT8. Clicoemodin showed the -7.5 KJ/mol binding energy with 4WE8 and 7NT8. Similarly, rumexoside showed the -7.6 KJ/mol binding energy with 4WE8 and -7.6 KJ/mol with 7NT8. Furthermore, Molecular dynamic simulation and MMPBSA binding free energy validated the stability of protein-ligand complexes. The current study suggested that clicoemodin and rumexocide are the promising inhibitors of H3N2 proteins hemagglutinin of influenza virus A and Influenza virus H3N2 nucleoprotein - R416A mutant, though there is further <i>in vitro</i> and <i>in vivo</i> validation is required.