The purpose of this service request for the Virology Division at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD is to expand on an identified multiple drugs and small molecules that inhibit alphavirus infection. The lead compounds identified will be further characterized by two specific aims: 1) define the mechanism of action of the lead compounds and 2) define the potency of the detected anti-alphavirus activity by a yield reduction assay and a rapid in vivo screen in mice. To address both specific aims, this effort will utilize infectious cDNA virus clones that express fluorescent or bioluminescent markers of infection, which allow for rapid assessment of virus activity in vitro and in vivo. Additionally, virus-like replicon particles (VRPs) expressing a fluorescent protein will be used to determine initially infected cells. These studies will allow for further selection of promising candidate therapeutics that warrant additional investigation for efficacy in vivo.

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