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 presently. 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.

中文翻译：

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N-乙酰半胱氨酸通过抑制病毒复制和炎症反应，有效缓解柯萨奇病毒B诱导的心肌炎。

柯萨奇病毒B（CVB）感染引起的病毒性心肌炎是一种严重的心肌炎性疾病，可能发展为心肌病和心力衰竭。目前尚无有效的特异性治疗方法。我们先前的研究表明，抑制促炎性caspase-1激活可有效抑制CVB复制。N-乙酰半胱氨酸（NAC）是一种广泛使用的抗氧化剂。在这项研究中，我们发现NAC在体内条件下可显着减轻CVB 3型（CVB3）引起的心肌损伤。重要的是，NAC处理同时抑制了心肌和细胞培养物中的病毒复制和炎症反应。NAC的抗病毒和抗发炎机制尽管独立于其抗氧化特性，却依赖于其对caspase-1激活的抑制作用。而且，NAC通过泛素蛋白酶体系统促进procaspase-1降解，这进一步促进了caspase-1的下调。NAC还抑制病毒蛋白酶的活性。两者合计，这项研究表明NAC通过靶向caspase-1发挥有效的抗CVB和抗炎作用。鉴于NAC是临床认可的药物，我们建议NAC作为CVB引起的病毒性心肌炎的有价值的治疗剂。