Abstract
Hand foot and mouth disease (HFMD) epidemic has occurred in many countries. Coxsackievirus A16 (CV-A16) and Enterovirus A71 (EV-A71) are the main causes of HFMD. Up to now, there are no anti-HFMD drugs available. Rupintrivir, a broad-spectrum inhibitor, is a drug candidate for HFMD treatment, while other HFMD inhibitors designed from several studies have a relatively low efficiency. Therefore, in this work we aim to study the binding mechanisms of rupintrivir and a peptidic α,β-unsaturated ethyl ester (SG85) against both CV-A16 and EV-A71 3C proteases (3Cpro) using all-atoms molecular dynamics simulation. The obtained results indicate that SG85 shows a stronger binding affinity than rupintrivir against CV-A16. Both inhibitors exhibit a comparable affinity against EV-A71 3Cpro. The molecular information of the binding of the two inhibitors to the proteases will be elucidated. Thus, it is implied that these two compounds may be used as leads for further anti-HFMD drug design and development.
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•SG85 and rupintrivir somewhat share a similar binding pattern to the 3C protease of CV-A16 and EV-A71.•SG85 shows a stronger binding affinity than rupintrivir against CV-A16.•Affinities of SG85 and rupintrivir are rather comparable for EV-A71.