Screening the potent compounds against enterovirus 71 and coxsackievirus A16 of hand, foot and mouse disease using steered molecular dynamics simulation

Abstract

Hand, foot and mouth disease (HFMD) outbreaks have occurred in many countries including Malaysia, China, Singapore, Vietnam, Brunei, Cambodia and England etc. In Thailand, increase in the prevalence of HFMD in children has forced many school to be closed across the outbreak. Enterovirus 71 (EV-71) and Coxsackievirus A16 (CV-A16) are two viruses that most commonly cause the pathogenic HFMD. Nowaday, many research groups have focused on drug design and development toward EV-71. However, compounds from study have relatively low efficiency. In this study, we aimed to screen the potent compounds from avialable databases and the rupintrivir analogs. Molecular docking was used to build the complex between ligand and CV-A16 protease. Then each complex was studied by steered molecular dynamics simulation (SMD) which shows better accuracy in screening the bioactivities compounds than molecular docking. Based on pulling force, the ZINC11783883 (583 kJ/mol•nm) was predicted to be a lead compound for further anti-HFMD drug design and development.