Biochanin A Exerts Broad-Spectrum Antiviral Activity Against Coronaviruses via Activating the AMPK/Nrf2/GSH Pathway

  • Microorganisms. 2026 Apr 9;14(4):851. doi: 10.3390/microorganisms14040851.
Qisheng Lin  1 ,  Fan Ji  1 ,  Haiyan Shen  2 ,  Jiajing He  1 ,  Donglan Liu  3 ,  Fang Li  4 ,  Ziyu Cheng  1 ,  Weisan Chen  5 ,  Fengxiang Zhang  6 ,  Zifeng Yang  3 ,  Jianxin Chen  1
Affiliations
  • 1. Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
  • 2. Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China.
  • 3. Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510320, China.
  • 4. State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, China.
  • 5. Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
  • 6. Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin 541004, China.
PMID: 42075248 DOI: 10.3390/microorganisms14040851
Abstract

Coronavirus infections pose a significant threat to both human and animal health, causing widespread morbidity, mortality, and substantial economic losses. While vaccines are crucial for prevention, their efficacy is often limited by the high mutation rate of these viruses. This underscores the urgent need for anti-coronavirus drugs, particularly broad-spectrum Antiviral agents. In this study, we demonstrated for the first time that Biochanin A (BCA), a bioactive isoflavonoid found in legumes, exhibits broad-spectrum Antiviral activity against coronaviruses. BCA potently inhibits porcine epidemic diarrhea virus (PEDV), as well as human coronaviruses HCoV-OC43 and HCoV-229E in vitro, with EC50 values of 6.90, 2.80 and 15.4 μM, respectively. In a lethal mouse model of HCoV-OC43-induced encephalitis, oral administration of BCA (40-60 mg/kg) significantly improved animal survival and reduced cerebral viral loads. Mechanistic studies revealed that BCA upregulates the AMPK/Nrf2 signaling pathway, thereby increasing expression of the glutamate-cysteine Ligase catalytic subunit (GCLC) and enhancing glutathione (GSH) biosynthesis. Our findings identify BCA as a promising host-directed Antiviral agent and highlight its therapeutic potential against coronavirus infections.

Keywords
AMPK/Nrf2/GSH pathway; antiviral activity; biochanin A; human coronavirus HCoV-229E; human coronavirus HCoV-OC43; porcine epidemic diarrhea virus.
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