Salvianolic acid A exerts antiviral effects by targeting the S protein, a virulence factor of porcine epidemic diarrhea virus

Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and high mortality in piglets, resulting in substantial economic losses to the global swine industry. However, effective antiviral therapeutics are still lacking. In this study, salvianolic acid A (SalA), a natural polyphenolic compound derived from <i>Salvia miltiorrhiza</i>, was identified as a potent inhibitor of PEDV through direct targeting of its spike (S1) protein. SalA efficiently suppressed viral replication, release, and infectivity <i>in vitro</i> and markedly alleviated intestinal damage, viral load, and clinical symptoms in infected piglets. Molecular docking and dynamic simulations further confirmed the stable binding between SalA and the S1 protein. Overall, this study provides the first comprehensive experimental evidence that SalA exhibits both prophylactic and therapeutic antiviral activities against PEDV, clearly highlighting its potential as a promising lead compound for the development of effective antiviral drugs to control PEDV and related coronavirus infections in livestock.