Extensive Virtual Screening of Neem-Derived Compounds as Potential Multifunctional Inhibitors for Human Metapneumovirus (HMPV): Neem-Derived Compounds against Human Metapneumovirus

Abstract

Human Metapneumovirus (HMPV) causes severe respiratory infections, yet no specific antiviral treatments exist. This study explores the antiviral potential of Neem-derived phytochemicals such as azadirachtin, gedunin nimbolinin, nimbin, nimbidin, nimbolide, salannin, and quercetin, against HMPV proteins using molecular docking, Non-Covalent Interaction (NCI) analysis, and molecular dynamics (MD) simulations. Docking results revealed strong hydrophobic interactions, hydrogen bonding, and salt bridge formation, stabilizing the ligand-protein complex. NCI analysis confirmed significant van der Waals and electrostatic interactions. MD simulations over 30 ns demonstrated complex stability, with persistent hydrogen bonding and minimal structural deviations. Principal component and free energy landscape (FEL) analyses highlighted stable equilibrium states, while root mean square deviation (RMSD) analysis confirmed structural integrity. These findings suggest that Gedunin the key constituent, strongly binds and stabilizes HMPV proteins, highlighting its potential as an antiviral candidate for further validation