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Published on: July 15, 2019
N-Acetyl cysteine effectively alleviates Coxsackievirus B-Induced myocarditis through suppressing viral replication
Yao Wang1, Shuoxuan Zhao1, Yang Chen2
1Department of Cell Biology, Harbin Medical University, 157 Baojian Road, Harbin, 150081, China.
Insights
N-acetyl cysteine (NAC) effectively treats viral myocarditis by inhibiting caspase-1 activation, reducing Coxsackievirus B replication and inflammation. This clinically approved drug offers a promising therapy for heart inflammation.
Area of Science:
- Virology
- Immunology
- Cardiology
Background:
- Viral myocarditis, often caused by Coxsackievirus B (CVB), leads to severe myocardial inflammation, potentially progressing to heart failure.
- Current treatments for viral myocarditis are limited, highlighting the need for effective therapeutic agents.
- Previous research indicated that inhibiting caspase-1 activation suppresses CVB replication.
Purpose of the Study:
- To investigate the therapeutic potential of N-acetyl cysteine (NAC) in treating CVB-induced viral myocarditis.
- To elucidate the mechanisms underlying NAC's antiviral and anti-inflammatory effects in the context of CVB infection.
Main Methods:
- In vivo studies using a mouse model of CVB type 3 (CVB3) infection.
- In vitro cell culture experiments to assess NAC's effects on viral replication and inflammatory markers.
- Analysis of caspase-1 activation, procaspase-1 degradation via the ubiquitin-proteasome system, and viral protease activity.
Main Results:
- NAC significantly alleviated myocardial injury in CVB3-infected mice.
- NAC suppressed both CVB replication and inflammatory responses in the myocardium and cell cultures.
- NAC's therapeutic effects were mediated by the inhibition of caspase-1 activation, independent of its antioxidant properties, and by inhibiting viral proteases.
Conclusions:
- N-acetyl cysteine (NAC) demonstrates potent antiviral and anti-inflammatory effects against Coxsackievirus B by targeting caspase-1 activation.
- NAC promotes procaspase-1 degradation and inhibits viral proteases, contributing to its therapeutic efficacy.
- Given its clinical approval and demonstrated efficacy, NAC is recommended as a potential therapeutic agent for viral myocarditis.
Abstract:
Viral myocarditis caused by Coxsackievirus B (CVB) infection is a severe inflammatory disease of the myocardium, which may develop to cardiomyopathy and heart failure. No effective specific treatment is available. Our previous study demonstrated that suppression of proinflammatory caspase-1 activation effectively inhibited CVB replication. N-acetyl cysteine (NAC) is a widely used antioxidant. In this study, we found that NAC significantly alleviated the myocardial injury caused by CVB type 3 (CVB3) under in vivo condition. Importantly, NAC treatment simultaneously suppressed viral replication and inflammatory response in both myocardium and cell culture. The antiviral and anti-inflammation mechanism of NAC, while independent of its antioxidant property, relies on its inhibition on caspase-1 activation. Moreover, NAC promotes procaspase-1 degradation via ubiquitin proteasome system, which further contributes to caspase-1 down-regulation. NAC also inhibits the activity of viral proteases. Taken together, this study shows that NAC exerts potent anti-CVB and anti-inflammation effect through targeting caspase-1. Given that NAC is a clinically approved medicine, we recommend NAC as a valuable therapeutic agent for viral myocarditis caused by CVB.
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