Discovery of Promising Antiviral Candidates Against Foot-and-Mouth Disease Virus Through Molecular Docking of 3C Protease Inhibitors

Abstract

Foot-and-Mouth Disease Virus (FMDV) is a highly contagious pathogen that threatens livestock health and global food security. The viral 3C protease (3C^pro) plays a crucial role in viral replication and represents a promising target for antiviral intervention. In this study, we employed molecular docking to evaluate the binding affinity and interaction profiles of selected small-molecule ligands against FMDV 3C^pro. Docking results revealed several compounds with strong binding affinities, notably Ligand1, which formed multiple stabilizing interactions with the catalytic dyad residues His46 and Cys163. Compounds Y and Z also demonstrated favorable binding profiles through hydrogen bonding, hydrophobic contacts, and π–π stacking within the active site. Comparisons with the reference inhibitor Rupintrivir indicated that some ligands exhibited superior or comparable binding strength, highlighting their potential as antiviral candidates. These findings provide theoretical evidence supporting the further in vitro and in vivo evaluation of these compounds, contributing to the development of novel therapeutic strategies against FMDV.