Derivatives of 2-Methyl Tetrahydrofuran-n-Carboxylic Acids Inhibiting Novel HA3 Subtype of Influenza A Virus Hemagglutinin

Abstract

The HA3 influenza (H3N2) influenza was originally found in 2011 and later appeared in January 2021. As per WHO report, H3N2 has the potential of causing a pandemic; therefore, an inhibitor for H3N2 should be designed. The hemagglutinin variants have typical 18 subtypes present in humans. Therefore, in the study, we generated the phylogenetic tree for understanding the similarity sequence between 18 subtypes and also the sequence of similarity was compared to H3N2. Thereafter, scaffold structures of FDA-approved Peramivir were generated, among which, four compounds were selected based on their drug-likeness and synthetic feasibility for performing docking and MD simulations. Theoretical evaluations, such as electronic, spectroscopic, binding energy, Root Mean Square Deviation (RMSD), Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET), were performed to validate the derived chemical structures and identify their potential of acting as drug compounds. In the present work, derivatives of 2-methyl tetrahydrofuran-[Formula: see text]-carboxylic acids show the inhibitory activity with H3N2 (PDB ID: 4WEA) with stable conformations.