A Cell Based HTS Approach for the Discovery of New Inhibitors of the H5N1 Virus

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DESCRIPTION (provided by applicant): Currently, there is no commercially available vaccine to protect humans against the highly pathogenic avian influenza H5N1 virus that is spreading across Asia, Europe, and Africa. Since humans have no immunity against any H5 viruses, the Centers for Disease Control and Prevention estimates that the economic impact of the next influenza pandemic could cost the United States billions of dollars, devastate the world economy and potentially kill one billion people worldwide. Thus, there is a critical need for antiviral drugs to supplement vaccine development and existing chemotherapeutics. A high throughput screening (HTS) approach provides an opportunity to screen large compound libraries. We have developed and validated a 384-well cell-based assay that measures CPE induced in Madin Darby canine kidney (MDCK) cells by influenza virus infection, using a luminescent-based detection system for signal endpoint. This molecular screen will provide the scientific community with an assay that allows for the rapid identification of potential inhibitors of influenza virus by evaluating large compound libraries in vitro. The proposed studies aim to gain access to the Molecular Libraries Screening Center Network (MLSCN) high throughput screening resources to facilitate the discovery of new molecular probes for the inhibition of avian influenza strain H5N1 virus. To achieve the objective of this proposal, the specific aim is to assist the MLSCN in transferring the validated HTS assay to the appropriate screening center and provide technical support for follow up confirmatory assays on single dose 'hits' from the primary assay in a HTS dose response format.