Abstract
Myocarditis is a common cause of dilated cardiomyopathy, one of the most important single causes of heart transplantation. Coxsackie B viruses (CBV) are considered to be the principal etiological agents of viral myocarditis and direct virus‐induced damage to the heart tissue has been suggested to be the main mechanism underlying myocarditis in the murine model [Horwitz et al. 2000 Nat Med 6:693–697]. We demonstrate that 2‐(3,4‐dichloro‐phenoxy)‐5‐nitrobenzonitrile (DNB), a compound that was earlier shown to exhibit broad‐spectrum anti‐picornavirus activity is also markedly active against CBV replication in primary human myocard fibroblast. To challenge the hypothesis of [Horwitz et al. 2000 Nat Med 6:693–697] we assessed whether DNB is able to prevent the development of CBV‐induced myocarditis in a murine model. Subcutaneous (s.c.) administration of DNB at 250 mg/kg/day, at multiple injection sites (m.i.s.), for a period of seven consecutive days (starting at 1 day before infection) to 4‐week old C3H‐mice resulted in a (i) 62% reduction in the number of myocarditis foci as compared to the untreated control animals (p = 1.7 × 10^−10^) and (ii) a concomitant reduction in viral titers in the heart. These findings indicate that selective inhibition of the replication of CBV may have a beneficial effect on the development of viral myocarditis and confirms that direct viral induced damage is the main mechanism underlying CBV‐induced myocarditis. Early diagnosis of virus‐induced myocarditis will likely be mandatory for an antiviral drug treatment regimen to achieve its greatest clinical benefit. J. Med. Virol. 72:263–267, 2004. © 2004 Wiley‐Liss, Inc.