Grant: Project Grant

Influenza viruses represent a severe public health threat worldwide, infecting 5-20% of the population each year, causing annual epidemics leading to ~500,000 deaths every year. Besides seasonal influenza, intermittent pandemic influenza poses the real threat of increased mortality and morbidity. The emergence of two highly pathogenic influenza strains with pandemic-potential H5N1 (2003) and H1N1 (2009), have infected millions with thousands of fatalities in the last decade alone. The recently established highly fatal and drug-resistant H7N9 strain (2013-2017) is an ominous trend. Current influenza vaccines have limited ability to prevent influenza infections and they must be updated every year as viral surface proteins change. It takes ~6 months after detection of a new strain to produce a new vaccine, and take another 2-6 weeks to be effective. WHO has estimated that an outbreak of a 1918-like pandemic influenza could claim the lives of >100 million people before a matching vaccine could be prepared. Under these circumstances, antiviral agents are the best possible intervention, which could limit the spread of infection, prevent hospitalizations and deaths. But current antiviral therapy remains inadequate because of limited efficacy, severe side effects and drug-resistance problems. Therefore, there is a real unmet need to discover new classes of drugs to treat highly contagious influenza infections. Our recent work has led to the discovery of a new family of potent and selective inhibitors of influenza virus that are also effective against drug-resistant strains. In the proposed work, we will investigate detailed properties of these promising molecules in cell culture and animal models, and discover their mechanisms of action. New approaches for the treatment of influenza infections will result from our work. Novel drugs may emerge which could be developed to reduce serious complications and mortality associated with influenza infections in Canada and worldwide.