In silico assessment of antiviral potentials – natural compounds against Nipah virus precursor glycoprotein

Abstract

This study investigates the potential antiviral properties of three natural compounds, Resveratrol, Berberine, and Quercetin, through their interactions with the Nipah virus F0 glycoprotein, a critical protein involved in viral fusion and entry.Employing molecular docking, molecular dynamics (MD) simulations, and MM/PBSA analysis, we assessed the binding affinity, structural stability, and thermodynamic profiles of these compounds in relation to the F0 glycoprotein.The structural quality of the F0 glycoprotein model was confirmed through PROCHECK analysis, ensuring its reliability for subsequent computational studies.Our docking results revealed Resveratrol as the most promising compound, exhibiting the strongest binding affinity and forming stable interactions, primarily through hydrogen bonds, with key residues of the glycoprotein.This suggests that Resveratrol could serve as an effective fusion inhibitor, potentially stabilizing the protein in a conformation that disrupts its function.Berberine showed moderate binding affinity but demonstrated a rich and diverse interaction profile, including - stacking and -cation interactions, indicating its potential as a stable, effective ligand.In contrast, Quercetin, while engaging multiple key residues, showed lower binding affinity and greater conformational flexibility, potentially limiting its efficacy as a standalone agent.MD simulations revealed that Resveratrol induced minimal structural fluctuations, maintaining a stable proteinligand complex, while Berberine exhibited moderate flexibility but still preserved overall protein integrity.Energetic analysis further indicated that Resveratrol had a more favourable binding free energy, suggesting it could act as a more potent and stable inhibitor of the F0 glycoprotein.These findings underscore Resveratrol's potential as a lead compound for the development of targeted antiviral therapies against Nipah virus and highlight the complementary antiviral potential of Berberine.This study lays the groundwork for future experimental validation and optimization of these compounds, positioning them as viable candidates in antiviral drug discovery.