Sodium Copper Chlorophyllin Is Highly Effective against Enterovirus (EV) A71 Infection by Blocking Its Entry into the Host Cell

Human enteroviruses (HEVs) pose an ongoing threat to global public health. Particularly, enterovirus-A71 (EV-A71), the main pathogen causing hand-foot-and-mouth disease (HFMD), has caused ongoing outbreaks globally in recent years associated with severe neurological manifestations and several deaths. Currently, no effective antivirals are available for the prevention or treatment of EV-A71 infection. In this study, we found that sodium copper chlorophyllin (CHL), a health food additive and an over-the-counter anticancer medicine or treatment to reduce the odor of urine or feces, exhibited potent inhibitory activity against infection by divergent EV-A71 and coxsackievirus-A16 (CV-A16) isolates at a low micromolar concentration with excellent safety. The antiviral activity of each was confirmed by colorimetric viral infection and qRT-PCR assays. A series of mechanistic studies showed that CHL did not target the host cell but blocked the entry of EV-A71 and CV-A16 into the host cell at the postattachment stage. In the mouse model, CHL could significantly reduce the viral titer in the lungs and muscles. Since CHL has been used in clinics for many years with excellent safety, it has the potential to be further developed into a prophylactic or therapeutic to prevent or treat HFMD caused by EV-A71 or CV-A16 infection.