Related Experiment Video

Updated: Jun 21, 2026

Use of Viral Entry Assays and Molecular Docking Analysis for the Identification of Antiviral Candidates against Coxsackievirus A16
06:03

Use of Viral Entry Assays and Molecular Docking Analysis for the Identification of Antiviral Candidates against Coxsackievirus A16

Published on: July 15, 2019

NAE inhibitor MLN4924 effectively suppresses Coxsackievirus B3 replication

Siwei Li1, Jianwei Wei2, Yanyan Dong2

  • 1Department of Cell Biology, School of Basic Medical Sciences, Harbin Medical University, 157 Baojian Road, Harbin, 150081, China; Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China; Heilongjiang Provincial Key Laboratory of Panvascular Disease, Harbin, 150086, China.

Microbial Pathogenesis
|June 19, 2026
PubMed

Insights

MLN4924, a neddylation inhibitor, shows potent antiviral effects against Coxsackievirus B (CVB) infection by targeting viral replication and boosting the immune response. This offers a promising therapeutic strategy for myocarditis and cardiomyopathy caused by CVB.

Area of Science:

  • Virology
  • Cardiology
  • Pharmacology

Background:

  • Myocarditis, often caused by Coxsackievirus B (CVB), is a major cause of dilated cardiomyopathy and sudden cardiac death.
  • Current treatment options for CVB-induced myocarditis are limited due to the lack of approved antiviral drugs.
  • Viral protein neddylation, specifically of the 3Dpol RNA-dependent RNA polymerase, enhances CVB replication.

Purpose of the Study:

  • To investigate the antiviral efficacy of MLN4924, a selective neddylation inhibitor, against CVB infection.
  • To explore the therapeutic potential of targeting viral protein neddylation for treating CVB-related cardiovascular diseases.

Main Methods:

  • In vitro and in vivo studies using CVB3 infection models.
  • Treatment with MLN4924, a selective neddylation inhibitor.
  • Assessment of viral replication, myocardial damage, inflammatory markers, and protein neddylation levels.
  • Analysis of nuclear factor erythroid 2-related factor 2 (NRF2) pathway modulation.

Main Results:

  • MLN4924 demonstrated potent antiviral activity against CVB3 with low cytotoxicity, particularly when administered early.
  • MLN4924 significantly inhibited viral replication in vitro and in the myocardium of infected mice.
  • Treatment alleviated myocardial damage and reduced inflammation.
  • MLN4924 suppressed 3Dpol neddylation and promoted its degradation, while upregulating NRF2 by inhibiting its ubiquitination.

Conclusions:

  • MLN4924 exhibits significant antiviral effects against CVB infection, both in vitro and in vivo.
  • Targeting viral protein neddylation with MLN4924 is a viable therapeutic strategy for CVB-induced myocarditis.
  • The antiviral mechanism involves inhibiting viral replication and modulating the host immune response via NRF2 upregulation.

Keywords:
Coxsackievirus BMyocarditisNAE inhibitorNeddylationNuclear factor erythroid 2-related factor 2

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