Core B, as part of the Program Project: SARS Coronavirus: Inhibition of Entry with Dr. K. V. Holmes as PI,will provide BSL3 support when required primarily for Projects #1, #2 and #6. The plan is to evolve Core Bfrom a laboratory dedicated to SARS work within the Bio-Environmental Hazards Research Building(BHRB) at the Foothills Campus of Colorado State University (CSU) in conjunction with a contract recentlyfunded by NIH for investigation of SARS as a new unit within a new research program on emerging viraldiseases administered by Dr. Barry Beaty at CSU. The new SARS laboratory is expected to be functioningbefore review of this proposal is completed.
Specific Aims for Core B: (1) Propagation, titration andpurification of SARS-CoV. (2) Assay antibody-mediated detection of virus infection in cells by viralcytopathic effects, immunofluoresence, immunocytochemistry or FACS bioanalyzer. (3) Assay antibody-mediated inhibition of binding or infection of live virus with permissive host cells. (4) Assay viral S peptide-mediated inhibition of binding or infection of live virus with permissive host cells. (5) Prepare tissues (e.g.brush border membranes) from a variety of species for binding studies with SARS-CoV. (6) Extract SARS-CoV RNA to aid cloning of receptor cDNA. (7) Test anti-viral drugs or vaccines that target SARS-CoV-receptor interactions in animals. Core B will have an integral role in the Program Project achieving the goalsof finding several complementary ways to block virus binding to susceptible cells and thereby prevent virusinfection. Improved diagnosis, treatment and control of SARS-CoV infection in humans are dependent uponlearning which cells or tissues bind the virus. Information derived from infection of naturally occurringsusceptible animal models, or transgenic mice with genetically induced susceptibility will be used to testexperimental treatment protocols that interfere with virus binding to receptors. The findings from theProgram Project are expected to provide guidance for treatment of SARS-infected humans.
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