Identifying potential compounds from Bacopa monnieri (brahmi) against Coxsackievirus A16 RdRp targeting HFM disease (tomato flu)

Abstract

Abstract The most promising drug target to treat hand, foot, and mouth disease (HFMD) caused by coxsackievirus (CVA16) is RNA-dependent RNA polymerase (RdRp). This study offered an in-silico pipeline to identify possible RdRp inhibitors against CVA16 RdRp. Here, 91 natural compounds derived from Bacopa monnieri (brahmi) were virtually screened against the RdRp of CVA16. Bacobitacin D, a hit screened in this study, exhibited eight hydrogen bonds with RdRp targeting catalytic site residues (Asp238 and Asp329). Later, the molecular dynamics (MD) simulation and MM/GBSA binding free energy calculations were performed with the top three hits selected on the exhaustive docking score (≤ -9.55 kcal/mole). Bacobitacin D showed the minimum fluctuation (< RMSD > = 0.75 nm, standard deviation = 0.02) over the 100 ns MD simulation time. However, the ΔGTOTAL binding free energy of Bacopaside IV was the lowest with − 23.70 kcal/mole while Bacobitacin D showed comparable ΔGTOTAL with − 19.14 kcal/mole. Later, the middle structures of the most populated cluster obtained from MD simulation were studied for the interaction. Bacobitacin D showed direct interaction with the catalytic residues (Asp238 and Ser289). This study proposed Bacobitacin D as active inhibitor against RdRp of CVA16 that need to be validated in an experiment to ascertain its inhibitory action.