2. Academic Validation
  3. Mycophenolate mofetil exerts broad-spectrum antiviral activity against coronaviruses including SARS-CoV-2

Mycophenolate mofetil exerts broad-spectrum antiviral activity against coronaviruses including SARS-CoV-2

  • Virol J. 2025 Mar 4;22(1):56. doi: 10.1186/s12985-025-02673-2.
Mengyuan Wu 1,  Kun Wang 1,  Huiqiang Wang 1,  Haiyan Yan 1,  Shuo Wu 1 2,  Ge Yang 1,  Yuhuan Li 3,  Yongsheng Che 4,  Jiandong Jiang 5
Affiliations

Affiliations

  • 1 CAMS Key Laboratory of Antiviral Drug Research, Beijing Key Laboratory of Technology and Application for Anti-Infective New Drugs Research and Development, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • 2 State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
  • 3 State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. yuhuanlibj@126.com.
  • 4 State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. cheys@im.ac.cn.
  • 5 State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. jiang.jdong@163.com.
PMID: 40038695 DOI: 10.1186/s12985-025-02673-2
Abstract

Background: New anti-coronavirus drugs are continuously being developed to address the serious long-term challenge posed by numerous SARS-CoV-2 variants. The clinical immunosuppressants mycophenolate mofetil (MMF) and mycophenolic acid (MPA) have been reported to have anti-coronavirus activities. However, systematic studies have not been conducted to evaluate their activities and mechanisms against pan-coronaviruses, including SARS-CoV-2.

Methods: The Antiviral effect of MMF and MPA was determined by qRT-PCR assay, Western blotting, and immunofluorescence assay. The IMPDH inhibition effect of MMF was determined by cellular thermal shift assay and Western blotting.

Results: We showed that MMF and MPA had broad-spectrum inhibitory effect against coronavirus, including HCoV-229E, HCoV-OC43, and SARS-CoV-2 ancestral strain and its variants. In terms of characteristics, MMF acted in the early stages of viral Infection and inhibited viral replication by blocking purine nucleotide synthesis through interaction with inosine-5'-monophosphate dehydrogenase (IMPDH). Therefore, the Antiviral effect of MMF can be reversed by exogenous guanosine. Additionally, MMF in combination with molnupiravir, GC376 or E64d showed synergistic Antiviral effects.

Conclusion: MMF and MPA exerted broad-spectrum anti-coronavirus effects by inhibiting IMPDH activity. MMF had a synergistic Antiviral effect when combined with Other drugs, showing its potential clinical Antiviral applications.

Keywords

Coronavirus; Drug combination; IMPDH; MMF; MPA; SARS-CoV-2.

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