Small Molecule Antiviral Agents Against Flaviviruses

Flaviviruses are a major health threat worldwide. This family of RNA viruses causes a variety of deadly diseases such as Dengue Fever, Yellow Fever, West Nile virus, and Tick-borne Encephalitis. There are currently no effective means to control these viruses. New drugs to counteract these viruses are desperately needed. Flaviviruses block the body's immune response by inhibiting nuclease enzymes which degrade viral RNA. Our goal is to identify small molecules to disrupt these flavivirus nuclease inhibitors to increase the cell's antiviral response. We will develop a high-throughput fluorescence polarization assay to identify novel small molecule disruptors of the viral inhibitor from compound libraries. We will also identify novel RNA-disrupting compounds using computer modeling techniques. The novel drugs identified will be synthesized and tested using flavivirus-infected cells in tissue culture to confirm biological activity.