AUTHOR=Sahoo Sthitaprajna , Lee Hak-Kyo , Shin Donghyun 

TITLE=Structure-based virtual screening and molecular dynamics studies to explore potential natural inhibitors against 3C protease of foot-and-mouth disease virus

JOURNAL=Frontiers in Veterinary Science

VOLUME=Volume 10 - 2023

YEAR=2024

URL=https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2023.1340126

DOI=10.3389/fvets.2023.1340126

ISSN=2297-1769

ABSTRACT=Foot-and-mouth disease (FMD) is a highly infectious animal disease caused by FMDV (foot-andmouth disease virus) and primarily infects cloven-hoofed animals like cattle, sheep, goats, pigs, etc. It has become a significant health concern in global livestock industries because of diverse serotypes, high mutation rates, and contagious nature. There is no specific antiviral treatment available for FMD. Hence, based on the importance of 3C protease in FMDV viral replication and pathogenesis, we have employed a structure-based virtual screening method by targeting 3C protease with a natural compounds dataset (n=69,040) from the InterBioScreen database. Virtual screening results identified five potential compounds, STOCK1N-62634, STOCK1N-96109, STOCK1N-94672, STOCK1N-89819, and STOCK1N-80570 with a binding affinity of -9.576 kcal/mol, -8.1 kcal/mol, -7.744 kcal/mol, -7.647 kcal/mol, and -7.778 kcal/mol respectively. The compounds were further validated through physiochemical properties and density functional theory (DFT). Subsequently, the comparative 300ns MD simulation of all five complexes exhibited overall structural stability from various MD analyses like RMSD, RMSF, Rg, SASA, Hbonds, PCA, FEL, etc. Furthermore, MM-PBSA calculation suggests all five compounds, particularly STOCK1N-62634, STOCK1N-96109, and STOCK1N-94672, can be considered as potential inhibitors because of their strong binding affinity towards 3C protease. Thus, we hope these identified compounds can be studied extensively to develop natural therapeutics for the better management of FMD.