Houttuynia cordata Extract Inhibits Coxsackievirus B3 Replication through Attenuation of Pyroptosis

Coxsackievirus B3 (CVB3) is a major pathogen causing viral myocarditis, and pyroptosis, an inflammatory form of programmed cell death, is emerging as a key mechanism in its pathogenesis.Although Houttuynia cordata (H.cordata) possesses various pharmacological properties, its direct antiviral effects against CVB3 and the mechanisms regulating CVB3-mediated pyroptosis have not been fully elucidated.Therefore, this study was conducted with the goal of confirming the antiviral effects of H. cordata extract using a CVB3 infection model.In CVB3 infection, treatment with H. cordata extract strongly inhibited viral replication by suppressing the synthesis of both positive-strand (viral genome) and negativestrand (replication intermediate) viral RNA.Consistent with these transcriptional inhibitory effects, Western blot analysis confirmed a dose-dependent significant decrease in the expression of VP1, a major viral capsid protein.Furthermore, the extract effectively preserved host protein synthesis mechanisms by inhibiting virusinduced eIF4G1 cleavage and blocking damage caused by potently inhibiting PARP cleavage.The H. cordata extract demonstrated potent cytoprotective effects by comprehensively blocking the CVB3-induced pyroptosis pathway.Additionally, the extract prevented the formation of membrane-terminal pores and inhibited the extracellular release of HMGB1 by inhibiting caspase-1 activation and gasdermin D (GSDMD) cleavage.By demonstrating the successful control of CVB3-induced pyroptosis, this study provides strong scientific grounds for the development of safe, natural product-derived therapeutics for CVB3 myocarditis and related severe inflammatory diseases.