ANTIVIRAL TREATMENT WITH WIN-54-954 REDUCES MORTALITY IN MURINE COXSACKIEVIRUS B3 MYOCARDITIS

Background Coxsackieviruses B (CBVs) are dominant causative agents in myocarditis and are associated with pathogenesis in some cases of dila ted cardiomyopathy, a clinical entity with a poor survival without hea rt transplantation. Methods and Results in vitro, the antiviral agent WIN 54 954 was shown to inhibit replication of CBV3 at a minimal inhib itory concentration value of 0.02 mg/L. Administration of WIN 54 954, 100 mg/kg BID PO, beginning on the day of infection resulted in comple te protection from enteroviral mortality (P<.01). WIN 54 954 treatment did not abrogate the inflammatory reaction in the myocardium. No diff erence was found in the expression of surface lymphocyte subset marker s. At 3 weeks, macrophages seemed to dominate the inflammatory reactio n, regardless of treatment. There was no difference in CBV3 antibody t iters, indicating that WIN 54 954 does not interfere with the developm ent of protective immunity. Complement factors C3 and B were synthesiz ed at a higher level during infection and correlated well with the deg ree of inflammatory reaction. Conclusions The results show that WIN 54 954 is a potent antiviral agent with a highly significant effect on s urvival in CBV-induced myocarditis in the A/J mouse if treatment is st arted early. It is suggested that the reduction in mortality seen with WIN 54 954 administration is due to an inhibitory effect on virus rep lication in affected organs that does not interfere with cellular or h umoral immunity.