Endophytic extract from Zanthoxylum piperitum as a promising source of anti-SARS-CoV-2 agents.

Endophytic fungi produce secondary metabolites that protect their host plants from external threats, and this symbiotic system represents a promising source of antiviral compounds. In this study, we evaluated the anti- severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity of culture extracts from endophytic fungi isolated from Zanthoxylum piperitum. Among the 12 isolates tested, six exhibited significant antiviral activity in SARS-CoV-2-infected cells, and three of these showed distinct inhibitory effects on the viral 3C-like (3CL) protease. Chemical analysis of the active extracts identified sapinopyridione-produced by a Botryosphaeria endophyte-as the principal active metabolite. This compound displayed potent anti-SARS-CoV-2 activity, with a half-maximal inhibitory concentration (IC50) of 2.45 μM (0.58 μg/mL). These findings suggest that sapinopyridione derivatives are promising lead compounds for the development of antiviral agents targeting SARS-CoV-2.