Grant: Proof of Principle Program - Phase I

An estimated one billion people get infected annually with seasonal influenza around the world, with 3-5 million severe cases and 500,000 deaths, especially in vulnerable populations such as children, the elderly, and immunocompromised people. Besides seasonal influenza, intermittent pandemic influenza poses real threats with increased mortality and morbidity. In the last century, the world has been severely hit by influenza pandemics three times (1918, 1957 and 1968). We have witnessed the emergence of two highly pathogenic influenza strains with pandemic-potential H5N1 (2003) and H1N1 (2009), which infected millions in the last decade alone. An outbreak of pandemic influenza similar to the 1918 Spanish flu could claim lives of more than 100 million young healthy people worldwide within a short period of time. Vaccines are available for preventing influenza infections; however, they have several limitations such as efficacy and availability, which is dependent on timely production and supply. Further, influenza vaccines must be updated every year since viral surface protein changes easily. Emerging resistance to currently available anti-influenza drugs undermines the desperate unmet medical need for discovery of novel anti-influenza drugs. Therefore, new classes of effective agents, working through different mechanisms, are urgently required. Recent research in our laboratory has led to the identification of a new family of compounds that are potent and selective inhibitors of various influenza virus strains. These molecules also possess activity against drug-resistant strains. The overall goals of the proposed research project are the investigation of the antiviral effectiveness of these promising agents in animal models that will advance our technology and develop commercializable candidate drugs for the treatment of influenza infections. These studies will provide a major impact on the health of Canadians and people worldwide.