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

作　　者：Parveen Punia Arun Prajapati Priyasha Maitra Avinash Mishra 

机构地区：[1]Pt.Neki Ram Sharma Government College,Rohtak,Haryana,124001,India [2]Growdea Technologies Pvt.Ltd.,Gurugram.,Haryana,122004,India

出　　处：《Medicine in Novel Technology and Devices》2023年第4期87-104,共18页医学中新技术与新装备（英文）

摘　　要：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(Asp^(238)and Asp^(329))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 lowestΔGTOTAL binding free energy(-23.70 kcal/mol),while Bacobitacin D displayed a comparableΔGTOTAL of19.14 kcal/mol.Structural interpretation of the most populated cluster derived from MD simulations showed direct interactions of Bacobitacin D with pivotal catalytic residues,including Asp^(238)and Ser^(289).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.

关 键 词：RNA-Dependent RNA polymerase Hand Foot And mouth disease Coxsackievirus Molecular dynamics simulation Molecular mechanics with generalized born andsurface area solvation binding free energy Virtual screening 

分 类 号：R512.5[医药卫生—内科学]