Repurposing SARS CoV 2 ligands identifies salvianolic acid C as potential antiviral candidate against human...

Human Metapneumovirus (HMPV) is a leading cause of respiratory tract infections worldwide, with no approved antiviral treatments or vaccines currently available. This study explores the potential of repurposing SARS-CoV-2 ligands as therapeutic agents against HMPV through a comprehensive computational approach. The present study investigates three ligands, Salvianolic Acid C, Mycophenolic Acid, and Aurintricarboxylic Acid for their binding affinity, stability, and interaction dynamics with the HMPV protein structure using molecular docking, molecular dynamics (MD) simulations, binding free energy calculations, and principal component analysis (PCA). The results revealed that Salvianolic Acid C formed the most stable complex with HMPV protein model, exhibiting consistent RMSD values (5-6 Å), low residual fluctuations, and a favorable binding free energy of -26.12 kcal/mol. Hydrogen bond analysis further supported its stability, with a 20.97% occupancy between GLU96 of HMPV protein model and Salvianolic Acid C. In contrast, Mycophenolic Acid and Aurintricarboxylic Acid demonstrated weaker binding and higher conformational heterogeneity. PCA and free energy landscape (FEL) analysis confirmed the stable binding mode of Salvianolic Acid C, with well-defined, deep energy basins, while the other ligands exhibited fragmented and less stable conformations. Furthermore, these findings highlight that Salvianolic Acid C as a promising candidate for anti-HMPV therapy, leveraging its stable binding and favorable thermodynamic properties. This study provides a foundation for the development of targeted antiviral treatments against HMPV protein model, addressing a critical unmet need in respiratory disease management for further experimental validation.