Related Experiment Video
Updated: Jun 21, 2026
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
Summary
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.
Related Concept Videos
01:25Inhibitors Of Virion Release
Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...
01:30Inhibitors of Viral Protein Synthesis
Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
01:19Inhibitors of Virion Maturation and Assembly
As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...
01:22Antiviral Nucleoside Inhibitors
Antiviral Nucleoside InhibitorsAntiviral nucleoside inhibitors are structural analogs of natural nucleosides that interfere with viral DNA or RNA synthesis. These compounds selectively target viral polymerases due to their resemblance to host nucleosides, thereby disrupting viral genome replication.Mechanism of Acyclovir ActionAcyclovir is a guanosine analog with a three-carbon acyclic side chain. It selectively targets herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2),...
01:25Inhibitors of Bacterial Protein Synthesis
Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
01:28Inhibitors of Bacterial DNA Synthesis
Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...