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<p>Through structure-based virtual screening, this study identified the botanical compound fangchinoline (FAN) as an inhibitor of the porcine aminopeptidase N (pAPN) receptor and evaluated its anti-transmissible gastroenteritis virus (TGEV) activity, mechanism, and safety. FAN exhibited potent antiviral efficacy against TGEV in PK-15 and IPEC-J2 cells (EC<sub>50</sub> = 2.862 μM and 3.670 μM, respectively), significantly reducing viral RNA copies and N protein expression while suppressing the upregulation of the inflammatory cytokines IL-6 and TNF-α. It also showed broad-spectrum potential by inhibiting PEDV (EC<sub>50</sub> = 2.243 μM). Mechanistic studies using a cellular thermal shift assay (CETSA) and drug affinity-responsive target stability (DARTS) confirmed that FAN can bind to pAPN, affecting its thermal and enzyme stability. Time-of-addition assays indicated that FAN interferes with both the early (attachment and internalization) and late replication phases of TGEV. In acute toxicity tests, FAN showed low toxicity (LD<sub>50</sub> in mice: 2060.23 mg/kg for males, 1481.93 mg/kg for females) and no mutagenic potential in the Ames test. Favorable pharmacokinetic parameters were also observed in rats. In conclusion, FAN exerts its anti-TGEV effect by targeting the critical pAPN receptor. Its plant origin, potent and broad-spectrum antiviral activity, elucidated mechanism, and promising safety profile support its further development as a lead compound for anti-coronavirus strategies.</p>

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Fangchinoline demonstrates efficacy against TGEV through pAPN binding, as determined by preliminary toxicity evaluation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月27日

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  • Siyi Hu,
  • Mengping Song,
  • Yulu Wang,
  • Jieying Zhang,
  • Defeng Wen,
  • Yanan Liu,
  • Juncheng Chen,
  • Jiali Wu,
  • Yanfei Tao,
  • Xu Wang

摘要

Through structure-based virtual screening, this study identified the botanical compound fangchinoline (FAN) as an inhibitor of the porcine aminopeptidase N (pAPN) receptor and evaluated its anti-transmissible gastroenteritis virus (TGEV) activity, mechanism, and safety. FAN exhibited potent antiviral efficacy against TGEV in PK-15 and IPEC-J2 cells (EC50 = 2.862 μM and 3.670 μM, respectively), significantly reducing viral RNA copies and N protein expression while suppressing the upregulation of the inflammatory cytokines IL-6 and TNF-α. It also showed broad-spectrum potential by inhibiting PEDV (EC50 = 2.243 μM). Mechanistic studies using a cellular thermal shift assay (CETSA) and drug affinity-responsive target stability (DARTS) confirmed that FAN can bind to pAPN, affecting its thermal and enzyme stability. Time-of-addition assays indicated that FAN interferes with both the early (attachment and internalization) and late replication phases of TGEV. In acute toxicity tests, FAN showed low toxicity (LD50 in mice: 2060.23 mg/kg for males, 1481.93 mg/kg for females) and no mutagenic potential in the Ames test. Favorable pharmacokinetic parameters were also observed in rats. In conclusion, FAN exerts its anti-TGEV effect by targeting the critical pAPN receptor. Its plant origin, potent and broad-spectrum antiviral activity, elucidated mechanism, and promising safety profile support its further development as a lead compound for anti-coronavirus strategies.