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

被引：0

作者：

Wu, Mengyuan ^{[1
]}

Wang, Kun ^{[1
]}

Wang, Huiqiang ^{[1
]}

Yan, Haiyan ^{[1
]}

Wu, Shuo ^{[1
,2
]}

Yang, Ge ^{[1
]}

Li, Yuhuan ^{[2
]}

Che, Yongsheng ^{[2
]}

Jiang, Jiandong ^{[2
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Biotechnol, CAMS Key Lab Antiviral Drug Res, Beijing Key Lab Technol & Applicat Antiinfect New, Beijing, Peoples R China

[2] Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Biotechnol, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China

来源：

VIROLOGY JOURNAL | 2025年 / 22卷 / 01期

基金：

中国国家自然科学基金;

关键词：

MMF; MPA; Coronavirus; SARS-CoV-2; IMPDH; Drug combination; RESPIRATORY SYNDROME CORONAVIRUS; ACID; INHIBITORS;

D O I：

10.1186/s12985-025-02673-2

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

BackgroundNew 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.MethodsThe 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.ResultsWe 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.ConclusionMMF 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.

引用

页数：13

共 45 条

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