Moracin M inhibits EV71 infection primarily by blocking viral attachment to host cells.

The global outbreak of hand, foot, and mouth disease (HFMD), mainly caused by enterovirus A71 (EV71) and coxsackievirus A16 (CA16) of the genus enterovirus, poses a serious threat to the health of young children, and severe neurological manifestations and associated symptoms are primarily attributed to EV71 infection. There is currently no specific antiviral drug available for HFMD. In this study, we identified Moracin M (MM), a flavonoid compound derived from Smilax china, as a potent inhibitor of EV71 and CA16 infection. Mechanistic investigation revealed that MM exerts its antiviral effects primarily by inhibiting viral attachment to host cells by targeting the virus. Furthermore, MM showed excellent safety and significant anti-EV71 activity in neonatal mice, and it also effectively suppressed the inflammatory response and alleviated muscle, lung, and brain tissue damage induced by EV71 infection. In conclusion, our study identified and demonstrated MM as a promising inhibitor of EV71 and CA16, providing important insights for the further development of MM as a potential therapeutic agent for HFMD caused by these viruses.