Grant: Operating Grant - Priority Announcement: Infection and Immunity (Bridge Funding)

Current antiviral therapeutic strategies target viral gene products. Although initially successful, the usefulness of these strategies is limited by their severe toxicity and susceptibility to circumvention by drug-resistant variants. In contrast, because of its central role in the proteolytic activation of numerous human viruses (e.g., HIV-1, West Nile virus, pandemic H5N1 influenza A), the cellular enzyme furin is a strategic target for antivirals. Our long-term goal is to develop a broadly effective therapy for those viral infections whose formation of infectious virus particles requires proteolytic maturation of viral envelope glycoproteins by furin. Because of our recent discovery of the most potent protein-based inhibitor of furin, we hypothesize that strategic manipulation of furin levels by our novel enzyme inhibitor, alone or in combination with other antivirals, may provide a means of inhibiting a large number of human viruses of great concern in Canada and around the world (e.g., HIV-1, West Nile virus, and highly pathogenic H5N1 influenza A virus).