N-Acetyl cysteine effectively alleviates Coxsackievirus B-Induced myocarditis through suppressing viral replication and inflammatory response

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 activati...

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Veröffentlicht in:Antiviral research 2020-07, Vol.179, p.104699-104699, Article 104699
Hauptverfasser: Wang, Yao, Zhao, Shuoxuan, Chen, Yang, Wang, Ying, Wang, Tianying, Wo, Xiaoman, Dong, Yanyan, Zhang, Jian, Xu, Weizhen, Qu, Cong, Feng, Xiaofeng, Wu, Xiaoyu, Wang, Yan, Zhong, Zhaohua, Zhao, Wenran
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Sprache:eng
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Zusammenfassung: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. •N-acetyl cysteine (NAC) shows antiviral and anti-inflammatory effect against Coxsackievirus B3 (CVB3) infection.•The antiviral mechanism of NAC is associated with its inhibition on caspase-1 and viral proteases.•NAC promotes the degradation of procaspase-1 through ubiquitin-proteasome pathway.
ISSN:0166-3542
1872-9096
DOI:10.1016/j.antiviral.2019.104699