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<p>Since the coronavirus disease 2019 (COVID-19) outbreak, research has been conducted on treatment and countermeasures against the causative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the development of new seeds is urgently needed because viruses have the characteristic of becoming resistant through mutation. We hypothesize that endophytes produce antiviral substances to combat foreign viruses in host plants. According to this hypothesis, the seeds of therapeutic agents for infectious diseases could be obtained from endophytes by culture experiments. This report found that <i>Aspergillus</i> sp. endophyte isolated from <i>Catharanthus roseus</i> produced ( +)-eupenoxide and its 3-ketone form with anti-SARS-CoV-2 activity. In addition, ( +)-eupenoxide-3,6-diketon was discovered as a new compound with potent 3C-like protease inhibitory activity (IC<sub>50</sub>: 0.048&#xa0;μM) by synthesis based on ( +)-eupenoxide. This finding could be an important evidence that endophytic fungi symbiosis with medicinal plants is useful as antiviral producers.</p> Graphical abstract <p></p>

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Potent SARS-CoV-2 3C-like protease inhibitor ( +)-eupenoxide-3,6-diketone (IC50: 0.048 μM) was synthesized based on ( +)-eupenoxide; lead from ( +)-eupenoxide analogs study by endophytic fermentation

  • 期刊论文

  • 发表日期：

    2025年2月3日

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  • Shoji Maehara,
  • Moeka Kumamoto,
  • Shogo Nakajima,
  • Yuhzo Hieda,
  • Koichi Watashi,
  • Toshiyuki Hata

摘要

Since the coronavirus disease 2019 (COVID-19) outbreak, research has been conducted on treatment and countermeasures against the causative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the development of new seeds is urgently needed because viruses have the characteristic of becoming resistant through mutation. We hypothesize that endophytes produce antiviral substances to combat foreign viruses in host plants. According to this hypothesis, the seeds of therapeutic agents for infectious diseases could be obtained from endophytes by culture experiments. This report found that Aspergillus sp. endophyte isolated from Catharanthus roseus produced ( +)-eupenoxide and its 3-ketone form with anti-SARS-CoV-2 activity. In addition, ( +)-eupenoxide-3,6-diketon was discovered as a new compound with potent 3C-like protease inhibitory activity (IC50: 0.048 μM) by synthesis based on ( +)-eupenoxide. This finding could be an important evidence that endophytic fungi symbiosis with medicinal plants is useful as antiviral producers.

Graphical abstract