Chlorogenic Acid Ameliorates CVB3-Induced Viral Myocarditis by Suppressing Viral Replication and ZBP1-Mediated PANoptosis

Viral myocarditis (VMC), predominantly driven by Coxsackievirus B3 (CVB3) infection and the resultant excessive immune response, lacks effective treatments and specific antiviral drugs in clinical practice. Chlorogenic acid (CGA) has been proven to have significant antiviral and anti-inflammatory properties. This study evaluated the potential and mechanism of action of CGA against CVB3-induced viral myocarditis. Our research results showed that CGA significantly alleviated myocardial tissue damage in vivo. This protective effect was accompanied by effective inhibition of myocardial inflammatory responses and viral replication. Further in vitro experiments confirmed that CGA significantly inhibited the replication of CVB3 in a dose-dependent manner, and its inhibitory effect mainly targeted the replication stage of the viral life cycle. Mechanistically, CGA treatment correlates with reduced ZBP1 expression and accelerated ZBP1 degradation involving the ubiquitin–proteasome pathway, accompanied by suppressed activation of PANoptosis markers. These findings suggest that CGA alleviates CVB3-induced myocarditis through concerted antiviral and anti-inflammatory effects, with ZBP1-mediated PANoptosis as a potential contributing mechanism.