Grant: China-Canada Joint Health Research Initiative

Viral myocarditis (heart muscle cell inflammation and injury) is one of the major heart diseases in our society, particularly in children and young adults. Epidemiological studies found that ~30% of the myocarditis cases are caused by coxsackievirus B3 (CVB3). This disease often enters its chronic phase, dilated cardiomyopathy (DCM). For patients with DCM, roughly half eventually require heart transplantation or die. There is no specific drug for treatment of CVB3 infections. In this international collaboration we, Dr. Dai (China) and Dr. Yang (Canada), will search for anti-CVB3 drugs by high-throughput screening (HTS) of a marine natural product library generated by Dr. Dai¿s lab. This library contains hundreds of thousands natural compounds produced by fermentation at different physiological conditions using >4000 microorganisms isolated from South China Sea and other under-explored environments. The quality of the library has been validated for its diversity, uniqueness and pharmacological activity. A HTS technique controlled by an automated robotic system will be used to screen this library against viral infection of culture cells or using a fluorescent reporter system targeting the viral gene. The primary drug candidates will be further de-overlapping by chemical analysis and then evaluated for anti-CVB3 activity by viral plaque assay on cell monolayers. The selected candidates will be further evaluated in Dr. Yang¿s lab using a viral myocarditis mouse model system, which includes evaluation of severity of myocarditis, determination of viral load in the heart and measurement of heart function of the mice. This study has great potential to discover novel drugs for the treatment of myocarditis and DCM.