Antiviral activity of Stephania japonica extract against porcine epidemic diarrhea virus infection

Porcine epidemic diarrhea virus (PEDV) is a major cause of diarrhea in piglets, causing substantial economic losses to the global swine industry. At present, no specific antiviral medications are available to treat PEDV infections. Natural compounds, with their wide availability, diverse biological activities, and low toxicity, have emerged as promising candidates for antiviral drug discovery. This study screened eight plant-derived bisbenzylisoquinoline alkaloids, including cepharanthine and tetrandrine, to assess their anti-PEDV activity in vitro. The results demonstrated that cepharanthine extracts significantly reduced viral titers and genome copies, indicating strong anti-PEDV activity. Notably, the botanical extracts exerted antiviral effects at both the initial stage of infection and the late phase of virion release, as evidenced by reduced viral output and suppressed mRNA synthesis. Molecular docking and dynamic analyses revealed that cepharanthine binds to PEDV 3CLpro (Mpro) protease through hydrogen bonds and hydrophobic interactions, forming a stable complex. This interaction likely impairs Mpro function, thereby inhibiting viral replication and the synthesis of related proteins. In vivo experiments further confirmed that piglets treated with cepharanthine extracts exhibited significantly lower viral loads and better preservation of intestinal structure compared to the control group. These findings provide key insights into the antiviral effects of cepharanthine extracts, supporting their potential for further development as anti-PEDV therapies and as a foundation for plant-derived antiviral compound research.