Antiviral activity of Mulberroside C against enterovirus A71 in vitro and in vivo

Enterovirus A71 (EV-A71) is one of the main causative agents of hand, foot and mouth disease which seriously threatens young children's health and lives. However, there is no effective therapy currently available for treating these infections. Therefore, effective drugs to prevent and treat EV-A71 infections are urgently needed. Here, we identified Mulberroside C potently against the proliferation of EV-A71. The in-vitro anti-EV-A71 activity of Mulberroside C was assessed by cytopathic effect inhibition and viral plaque reduction assays, and the results showed that Mulberroside C significantly inhibited EV-A71 infection. The downstream assays affirmed that Mulberroside C inhibited viral protein and RNA synthesis. Furthermore, Mulberroside C effectively reduced clinical symptoms in EV-A71 infected mice and reduced mortality at higher concentrations. The mechanism study indicated that Mulberroside C bound to the hydrophobic pocket of viral capsid protein VP1, thereby preventing viral uncoating and genome release. Taken together, our study indicated that Mulberroside C could be a promising EV-A71 inhibitor and worth extensive preclinical investigation as a lead compound.