Plantago lanceolata extract inhibits porcine epidemic diarrhea virus and emerging enveloped viruses by interfering with virus internalization in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Plantago lanceolata is a widely distributed perennial herb that has traditionally been used for the treatment of gastrointestinal disorders and upper respiratory tract diseases, as well as for wound and skin care. However, its antiviral activity against porcine epidemic diarrhea virus (PEDV) has not yet been elucidated.

AIM OF THE STUDY: In the present study, we analyzed the antiviral potential of Plantago lanceolata (PL) extract against PEDV and emerging enveloped viruses and identified its underlying mechanisms.

MATERIALS AND METHODS: The cytotoxicity and antiviral activity of PL extract against PEDV were evaluated. Mechanistic studies were conducted using time-of-addition and stage-specific assays. Furthermore, pseudotyped viruses bearing glycoproteins from various enveloped viruses were used to evaluate the effect of PL extract on viral entry.

RESULTS: Compared with ribavirin, Plantago lanceolata extract had stronger antiviral activity, with an IC50 of 5.64 μg/mL. Mechanistic analyses demonstrated that Plantago lanceolata extract inhibits PEDV entry by targeting the post-binding internalization step without affecting viral binding. Using confocal analysis, we revealed that PL extract inhibits both clathrin- and caveolin-mediated endocytosis. Its antiviral effect was abolished by trypsin, indicating the involvement of the endosomal entry pathway. The PL extract inhibited the entry of several pseudotyped enveloped viruses, which entered via endocytosis.

CONCLUSION: PL extract inhibits PEDV infection by interfering with viral internalization, suggesting that it may interfere with endocytic viral entry processes.