Exploiting Common Replication Steps to Discover and Develop Broad Spectrum Inhibitors of Flaviviruses

Flaviviruses, including dengue virus (DENV), Hepatitis C Virus (HCV), West Nile virus (WNV) and yellow fever virus (YFV), cause human disease on a global scale. Currently, there are no antiviral therapies for infection with these viruses or for other emerging members of the flavivirus family (Japanese Encephalitis, St. Louis Encephalitis and Tick-Borne Encephalitis for example). In this project, we will pursue a comprehensive strategy to develop broad spectrum antiviral drugs that may be effective against two or more flaviviruses.

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Discovery and Development of Inhibitors of Virally Encoded RNA Polymerases

The goal of this project is to identify competitive, alternative substrate inhibitors of virally encoded RNA dependent RNA polymerases (RdRps) with broad-spectrum antiviral activity against RNA viruses from multiple taxonomic families, including Paramyxoviridae, Bunyaviridae, Flaviviradae, Togaviridae, and Coronaviridae. The RdRps are functionally and structurally conserved among RNA viruses and consequently are good targets for generating broadly active therapeutic agents.

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Small-Molecule Therapeutics against Priority Myxovirus Pathogens

July 8, 2013

The goal of this project is to develop host-directed inhibitors of myxovirus replication that are designed to transform the prevalent one-drug, one-bug approach of antiviral therapy to a one-drug, multiple-bugs paradigm. This approach aims to systemically address two major challenges frequently associated with viral therapeutics: pre-existing or rapidly developing resistance to the inhibitor, and the narrow spectrum of activity associated with the majority of antiviral drugs.

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