Disrupting Viral Replication in Human Metapneumovirus: Targeting Key Proteins with Unani Phytochemicals through Structural Dynamics and Energetics

Abstract

Emerging viral infections pose significant global health challenges, necessitating the exploration of novel antiviral therapeutics. This study investigates the antiviral potential of bioactive compounds derived from the Unani system of medicine, leveraging molecular docking, molecular dynamics simulations, pharmacokinetic profiling, and quantum chemical calculations to assess their efficacy against the Human Metapneumovirus (HMPV) target protein (PDB ID: 5WB0).Molecular docking studies revealed that Crocin (-9.5 kcal/mol), Quercetin (-9.3 kcal/mol), and Oleuropein (-9.0 kcal/mol) exhibited remarkable binding affinities, engaging in multiple hydrogen bonds and hydrophobic interactions, comparable to standard antiviral drugs Remdesivir (-9.2 kcal/mol) and Favipiravir (-8.8 kcal/mol). These findings were further supported by molecular dynamics simulations, where Crocin and Quercetin maintained exceptional binding stability (RMSD ~1.8 [A], MM-PBSA energy ~ -80.5 kcal/mol), reinforcing their potential as HMPV inhibitors.Additionally, pharmacophore modeling and electronic structure analysis highlighted strong hydrogen bonding capacity, dipole moment, and electrostatic potential for these bioactives, facilitating optimal target interactions. Pharmacokinetic and toxicological assessments confirmed their high bioavailability, metabolic stability, and minimal toxicity, positioning them as promising candidates for further drug development.Overall, this comprehensive computational study underscores the therapeutic relevance of Unani-derived compounds, paving the way for natural antiviral interventions. Future in vitro and in vivo investigations will be essential to validate their clinical efficacy and optimize their drug-like properties.