Inhibition of coxsackie B3 virus induced myocarditis in mice by 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile.

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 x 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.

• Authors: Elizaveta Padalko, Erik Verbeken, Erik De Clercq, Johan Neyts
• Journal: Journal of medical virology (J Med Virol) Vol. 72 Issue 2 Pg. 263-7 (Feb 2004) ISSN: 0146-6615 [Print] United States
• PMID: 14695668 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2004 Wiley-Liss, Inc.

Chemical References

• Nitriles
• 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile

Topics

• Animals
• Cells, Cultured
• Chlorocebus aethiops
• Disease Models, Animal
• Enterovirus B, Human (drug effects)
• Enterovirus Infections (drug therapy, virology)
• Humans
• Mice
• Mice, Inbred C3H
• Myocarditis (drug therapy, virology)
• Nitriles (administration & dosage, pharmacology, therapeutic use)
• Vero Cells
• Virus Replication (drug effects)