Research Projects

Theme 2

RP008  Frueh

Dengue fever, West Nile disease, yellow fever and Japanese encephalitis are all caused by closely-related viruses (members of a group called Flaviviruses). Flaviviruses are transmitted to humans by mosquitoes, and together cause major international public health problems. Flaviviral infections cause hundreds of thousands of hospitalizations and tens of thousands of deaths per year. No drugs exist to treat people suffering from any of these diseases. PNWRCE project RP 008 has two inter-related goals. The first goal is to identify novel drugs that are effective against dengue virus, and hopefully against other flaviviruses as well. Our strategy will be to target host (human) proteins involved in dengue virus replication.  Specifically, we will be targeting a group of enzymes named protein kinases, which are known to play important roles in modifying cellular proteins involved in viral replication. We will screen small molecule libraries which have been specially designed to contain thousands of compounds that are each capable of inactivating one or more of the approximately 500 human protein kinases. The screening will take place at the Memorial Sloane Kettering Cancer Research Center state-of-the-art High-Throughput Screening facility in New York City. We hope to identify kinase-specific compounds which are able to suppress viral replication, yet do not cause ill-effects to the host cells in which the virus replicates. The second goal is to use the drugs discovered in the first goal as research tools to better understand the mechanisms by which flaviviruses cause disease in infected cells. It is hoped that this project will produce both new therapeutic strategies as well as a better understanding of the molecular mechanics of dengue virus pathogenesis.