Fungal Compound Sapinopyridione Shows Anti-SARS-CoV-2 Activity in Cells

A compound produced by an endophytic fungus isolated from Zanthoxylum piperitum shows potent activity against SARS-CoV-2 in infected cells, according to a study published in The Journal of Antibiotics on 23 October 2026. Shoji Maehara, Chiho Takahara, Ryo Watanabe, Serino Yoshitake, Toshiyuki Hata and colleagues, working with Shogo Nakajima, Hirofumi Ohashi and Koichi Watashi, isolated endophytic fungi from the plant and evaluated the anti-SARS-CoV-2 activity of their culture extracts. Of the 12 fungal isolates tested, six produced culture extracts that exhibited significant antiviral activity in SARS-CoV-2–infected cells.

Three of these six active extracts also showed distinct inhibitory effects on the viral 3C-like (3CL) protease, indicating that the extracts act on a defined viral enzyme in addition to their broader antiviral activity in the cell-based assays. Chemical analysis of the active extracts identified sapinopyridione as the principal active metabolite. The compound is produced by a Botryosphaeria endophyte recovered from Zanthoxylum piperitum.

In the infected-cell experiments, sapinopyridione displayed potent anti-SARS-CoV-2 activity, with a half-maximal inhibitory concentration (IC50) of 2.45 μM, equivalent to 0.58 μg/mL. The researchers report that this potency makes the compound a notable candidate among the metabolites recovered from the fungal collection. The study was motivated by the observation that endophytic fungi produce secondary metabolites that protect their host plants from external threats, a symbiotic system the authors describe as a promising source of antiviral compounds.

By screening culture extracts rather than individual purified molecules from the outset, the team could link antiviral activity in infected cells to specific fungal isolates and then narrow down the responsible metabolite through chemical analysis. The authors conclude that sapinopyridione derivatives are promising lead compounds for the development of antiviral agents targeting SARS-CoV-2. The findings rest on cell-culture experiments with a limited set of 12 isolates from a single plant species, so they do not establish efficacy in humans.

Subject of Research: Anti-SARS-CoV-2 activity of endophytic fungal extracts and sapinopyridione from Zanthoxylum piperitum

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

Article References: Maehara, S., Takahara, C., Watanabe, R., Yoshitake, S., Nakajima, S., Ohashi, H., Watashi, K., & Hata, T. (2026). Endophytic extract from Zanthoxylum piperitum as a promising source of anti-SARS-CoV-2 agents. The Journal of Antibiotics. https://doi.org/10.1038/s41429-026-00970-8

Image Credits: AI Generated

DOI: 10.1038/s41429-026-00970-8

Keywords: SARS-CoV-2, endophytic fungi, Zanthoxylum piperitum, sapinopyridione, Botryosphaeria, 3CL protease, antiviral compounds, natural products, secondary metabolites, drug discovery, The Journal of Antibiotics, Endophytic