Grant: Operating Grant

Hepatitis B virus (HBV) infection is a serious global health problem, with more than 400 million chronically infected individuals in the world. Estimates indicate that at least 2 billion people worldwide have been infected with HBV. Chronic HBV infection leads to liver damage, cirrhosis and liver cancer with high mortality, and 1.2 million deaths/year are attributed to HBV. In North America, ~300,000 new cases occur each year, resulting in ~43,000 chronic infections and 3,000 deaths. HBV infections (400 million) outnumber the HIV/AIDS cases (~33 million), and are a major medical problem worldwide. Alarmingly, HBV is far more infectious than HIV, especially following mucosal contact. Current antiviral therapy remains inadequate due to limited efficacy, severe side effects, rapid development of resistance and most importantly viral recurrence with exacerbation of liver pathology after cessation of therapy. Therefore, there is a real unmet need to discover new classes of efficacious and non-toxic anti-HBV drugs that can bring more complete virus suppression, reduce toxicity and avoid drug resistance problems. We have recently discovered new families of potent inhibitors of HBV that are also effective against drug-resistant HBV, a significant issue in HBV therapy. In the proposed work, we will investigate detailed antiviral properties in animal models, and understand mechanism of action of these promising agents. The proposed studies will delineate new approaches for the treatment of chronic HBV infections. Novel agents may emerge from these studies, which could then be developed as a new generation of efficacious antiviral drugs to combat drug resistance, and improve the life expectancy and quality of life of the HBV infected people in Canada and worldwide.