Pharmacological inhibition of neddylation by MLN4924 protects against Coxsackievirus B3-induced myocarditis.

Authors

Wenwen Shen, Wenwen Chen, Sun Yu, Mengyu Huang, Jialin Zhao, Jiapeng Gao, Wei Xu, Chunyang Xu, Limei Zhao, Min Li

Published in

Biochemical pharmacology. Pages 118282. Jul 25, 2026. Epub Jul 25, 2026.

Abstract

Viral myocarditis (VMC), predominantly caused by Coxsackievirus B3 (CVB3), remains a leading cause of sudden cardiac death and heart failure in young individuals. VMC results from both direct viral cytopathic effects and subsequent immune-mediated myocardial injury, yet effective antiviral therapies remain limited. MLN4924 (pevonedistat), a first-in-class neural precursor cell expressed developmentally downregulated 8 (NEDD8)-activating enzyme inhibitor, has been extensively characterized for its anti-proliferative and anticancer activities, though its antiviral potential in vivo remains largely unexplored. Here, we report that pharmacological inhibition of neddylation with MLN4924 confers robust protection against CVB3-induced myocarditis in mice, significantly improving cardiac function and survival. MLN4924 treatment also markedly reduced viral replication in the heart. Mechanistically, eukaryotic translation initiation factor 4G (eIF4G) was identified as a candidate MLN4924-responsive host factor. MLN4924 attenuated the CVB3-induced loss of eIF4G protein, a change that may contribute to the suppression of CVB3 internal ribosome entry site (IRES)-driven translation and viral protein synthesis. Collectively, our findings support MLN4924 as a promising antiviral candidate for the treatment of VMC.

PMID:
42501872
Bibliographic data and abstract were imported from PubMed on 26 Jul 2026.

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