N-Acetyl Cysteine Alleviates Coxsackievirus B-Induced Myocarditis by Suppressing caspase-1

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 medicine is available to treat CVB infection. Here we evaluated the anti-CVB effect of N-acetyl cysteine (NAC), a widely used antioxidant. NAC significantly alleviated myocarditis and improved the overall condition of CVB type 3 (CVB3)-infected mice. Importantly, NAC treatment suppressed viral replication in both myocardium and cell culture. We show that NAC inhibited CVB3 replication when it was applied at the early stage of CVB3 infection. NAC’s antiviral mechanism, while independent of its antioxidant property, relies on its inhibition on caspase-1 activation, since the knockdown of caspase-1 blocked CVB3 replication. Moreover, NAC promotes procaspase-1 degradation via ubiquitin proteasome system, which may further contribute to the inhibited activity of caspase-1. NAC also inhibits the activity of viral proteases. Taken together, this study shows that NAC exerts potent anti-CVB effect by inhibiting caspase-1 and viral proteases. This study suggests that NAC can be a safe therapeutic option for CVB-induced myocarditis.