Medicine in Novel Technology and Devices (Dec 2023)
Identifying potential compounds from Bacopa monnieri (brahmi) against coxsackievirus A16 RdRp targeting HFM disease (tomato flu)
Abstract
Hand, foot, and mouth disease (HFMD), primarily instigated by Coxsackievirus A16 (CVA16), poses a serious health concern, necessitating effective therapeutic interventions. The RNA-dependent RNA polymerase (RdRp) of CVA16 emerges as a promising drug target for HFMD treatment. This study presents an in-silico pipeline for the identification of potential RdRp inhibitors against CVA16. A library of 91 natural compounds derived from Bacopa monnieri (brahmi) was virtually screened against the CVA16 RdRp. Here, Bacobitacin D emerged as a promising hit molecule, forming 8 hydrogen bonds including key catalytic site residues (Asp238 and Asp329) within the RdRp active site. Further, molecular dynamics (MD) simulations and MM/GBSA binding free energy calculations was applied on the top three hits that were selected based on exhaustive docking scores (≤−9.55 kcal/mol). Bacobitacin D exhibited sustainable stability, as evidenced by minimal deviation (RMSD = 0.75 ± 0.02 nm) during a 100 ns MD simulation. Importantly, Bacopaside IV exhibited the lowest ΔGTOTAL binding free energy (−23.70 kcal/mol), while Bacobitacin D displayed a comparable ΔGTOTAL of −19.14 kcal/mol. Structural interpretation of the most populated cluster derived from MD simulations showed direct interactions of Bacobitacin D with pivotal catalytic residues, including Asp238 and Ser289. This comprehensive study confirmed Bacobitacin D as a potent inhibitor of CVA16 RdRp, offering a potential avenue for therapeutic intervention against HFMD. Experimental validation is required to confirm the inhibitory action of Bacobitacin D against HFMD.