THERAPY OF COXSACKIE-VIRUS B3-INDUCED MYOCARDITIS WITH WIN 54954 IN DIFFERENT FORMULATIONS

The antiviral efficacy of WIN 54954 was demonstrated in vivo in a Coxs ackie B 3 virus (Woodruff strain) induced myocarditis mouse model. The model was selected because of the high mortality rate during the firs t week, which was convenient for antiviral therapy regimen studies. Th e antiviral component WIN 54954 was found to inhibit the early virus-i nduced mortality almost completely if treatment was started at the sam e time as virus was inoculated. However, there was still a late mortal ity, ocurring at 1-2 months after virus inoculation. Non-infected mice which were treated with the drug did not show any such late effects. However, drug treatment in non-infected mice did not cause any mortali ty. When therapy was delayed for one day, 85% survived for 3 weeks as compared to 100% mortality after just over 3 weeks in the infected con trol group (p<4.05). With a delay of 4 days after viral inoculation, a therapeutic effect was still noted. Thus, mortality was virtually abr ogated when the compound was given early, but the effect vanished with time of delay. Different preparations of the WIN 54954 substance were tried, and it was found that a fat emulsion containing several nutrie nts (Nutrodrip(R)) was superior to other used formulations. We conclud e that the use of the antiviral drug WIN 54954 in treatment of enterov iral associated diseases is of great value if therapy is started early . Thus therapy is almost fully effective within 24 hours of infection, but the beneficial effects decline with time. Nutrodrip(R) oil emulsi on was found superior as vehicle as compared to other formulations. WI N 54954 is thus an interesting prototype drug in the treatment of ente roviral-mediated diseases, but further evaluation is needed to meet th e requirements in future potential clinical settings.