Soluble Coxsackievirus B3 3C Protease Inhibitor Prevents Cardiomyopathy in an Experimental Chronic Myocarditis Murine Model

Abstract Background Coxsackievirus B3 (CVB3) is a common cause of myocarditis and dilated cardiomyopathy. CVB3 3C protease (3CP) cleaves the viral polyprotein during replication. We tested whether a water soluble 3CP inhibitor (3CPI) had antiviral effects in a chronic myocarditis model. Methods Chronic myocarditis was established using DBA/2 strain mice. Starting on post-infection (p.i) day 3, CVB3-infected mice ( n  = 41) were treated with 3CPI by daily intraperitoneal (i.p.) injection at a concentration of 50 μM (1.7 mg/kg/day) per day for 3 consecutive days. Additional mice ( n  = 49) were injected with PBS as a control. Results The 5-week survival rate was significantly higher with 3CPI treatment (82.3% versus 47.9%; P P P P Conclusions Water soluble 3CPI was delivered through i.p. injection after CVB3 infection. This agent preserved heart function and decreased organ viral titers and myocardial damage. Soluble 3CPI may be beneficial in the treatment of cardiomyopathy associated with enterovirus infection.