JOURNAL OF BACTERIOLOGY AND VIROLOGY ISSN:1598-2467(Print) 2093-0429(Online)

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 negative-strand (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 virus-induced 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.