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

作者：Zhaoran Zhang, Yan Zeng, Yaning Lv, Xiaodan Li, Jiaqi Liu, Ziyi Zhang, Ze Tong, Wenqi Dong, Di Liu, Chen Tan, Chenchen Wang · 发表于：Journal of Virology · 年份：2026 · DOI：10.1128/jvi.02043-25 · 被引用次数：1 · 研究领域：Animal Virus Infections Studies、SARS-CoV-2 and COVID-19 Research、Immune responses and vaccinations

ABSTRACT Porcine epidemic diarrhea virus (PEDV), a member of the Coronaviridae family, infects the small intestinal epithelial cells of pigs, causing porcine epidemic diarrhea (PED), which is particularly severe in young piglets. Owing to its strong immunogenicity, the S1 subunit of the PEDV spike (S) protein mediates viral invasion by recognizing host cell receptors and inducing neutralizing antibodies. However, effective antiviral drugs against PEDV are lacking, and current control measures are limited. In this study, the truncated S1 protein was expressed and used in surface plasmon resonance screening of 416 natural compounds. Salvianolic acid A (SalA) exhibited the strongest antiviral activity against PEDV, with a dissociation constant KD of 4.54 × 10⁻⁷ M. Molecular docking revealed multiple hydrogen bonds between SalA and key amino acid residues of the S1 protein. In vitro assays demonstrated that SalA significantly reduced viral RNA copy number, titer, and N protein expression in a dose-dependent manner. SalA inhibited viral adsorption, replication, and release and showed direct virucidal activity. In a piglet challenge model, SalA treatment improved survival, alleviated clinical symptoms and intestinal lesions, and reduced viral loads in blood, feces, and tissues. Overall, SalA was identified as a potent natural compound that targets the PEDV S1 protein and exhibits strong antiviral effects both in vitro and in vivo , highlighting its promise as a therapeutic candidat...