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

RNA viruses cause the vast majority of viral infections in humans. Despite their medical importance, there are very few therapeutic options to treat infections caused by these viruses. Conventional anti-viral therapies that target viral enzymes have met with limited success because RNA viruses exhibit a high mutation rate, which leads to drug resistance. Our laboratory is focused on identifying anti-viral targets for West Nile virus and Dengue virus. Globally, these viruses infect up to 100 million people each year. Because they are "gene poor", RNA viruses encode very few proteins, often less than 10. Research from our laboratory and others, indicates that RNA virus proteins are multifunctional and interact with a surprisingly large number of host cell proteins. From a health perspective, these host proteins may be targets for anti-viral therapy. In theory, viruses should not develop resistance as quickly to drugs that target host cell proteins. To serve as anti-viral targets though, it must be possible to inhibit the activities of these host proteins through pharmaceutical intervention without major toxicity. This is of course the basis for most drugs in use today. The exciting part is that in theory, the simpler the virus, the more host proteins that are required for replication and dissemination, each of which represents a potential target for therapeutic intervention.