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

IF 4 3区医学 Q2 VIROLOGY Virology Journal Pub Date : 2025-03-04 DOI:10.1186/s12985-025-02673-2

Mengyuan Wu, Kun Wang, Huiqiang Wang, Haiyan Yan, Shuo Wu, Ge Yang, Yuhuan Li, Yongsheng Che, Jiandong Jiang

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引用次数: 0

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.

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来源期刊

Virology Journal 医学-病毒学

CiteScore

7.40

自引率

2.10%

发文量

186

审稿时长

1 months

期刊介绍： Virology Journal is an open access, peer reviewed journal that considers articles on all aspects of virology, including research on the viruses of animals, plants and microbes. The journal welcomes basic research as well as pre-clinical and clinical studies of novel diagnostic tools, vaccines and anti-viral therapies. The Editorial policy of Virology Journal is to publish all research which is assessed by peer reviewers to be a coherent and sound addition to the scientific literature, and puts less emphasis on interest levels or perceived impact.