The Chiral Isomers of Chlorogenic Acid Exert Distinct Antiviral Effects on Coxsackievirus A16 Infection

Coxsackievirus A16 (CVA16) is one of the major pathogens responsible for hand, foot, and mouth disease (HFMD), for which no specific antiviral therapy is currently available. Neochlorogenic acid (NCGA) and chlorogenic acid (CGA) are a pair of chiral isomers with highly similar chemical structures. While the antiviral activity of CGA has been extensively investigated, that of NCGA remains largely unexplored. In our study, we found that NCGA exhibited antiviral activity against CVA16, whereas CGA was completely inactive. Notably, NCGA also displayed extremely low cytotoxicity, and its antiviral efficacy was further confirmed in vivo. We further identified RNA-binding motif protein 24 (RBM24) as a host factor involved in the antiviral effect of NCGA against CVA16, as its knockdown attenuated the antiviral activity of NCGA. Collectively, our findings not only identify a novel natural product against CVA16 but also provide clues for the discovery of host factors involved in CVA16 infection.