Investigation of the therapeutic potential of oxysterols in SARS-CoV-2 infection
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Principal Investigator: Michael B Fessler Organization: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES Fiscal Year: 2020 Award: $56,896 Funding agency: National Institute of Environmental Health Sciences This project was funded earlier this summer (2020). To date, we have already: 1) contracted with Avanti Lipids to synthesize enantiomeric 25-hydroxycholesterol (25HC), which will be used as a control for 25HC to help distinguish protein-targeted vs. non-protein-targeted (membrane) effects of this oxysterol in our studies. 2) posted an advertisement to hire a postdoctoral fellow to conduct the proposed studies, and, to date, have received several applications. 3) completed studies of the effect of 25HC on infection of MRC-5 cells with HCoV-229E, an alternate endemic human coronavirus. 4) collaborated with the NIEHS Viral Vector Core Laboratory to begin construction of a SARS2 Spike protein pseudovirus with B-lactamase payload that can be used to assay virus-cell fusion. 5) commenced efforts to isolate a high-ACE2-expressing subclone of Calu-3 cells for future infection studies. Terms: <2019 novel coronavirus><2019-nCoV><25-hydroxycholesterol><Address><Advertisements><Anti-Inflammatories><Anti-Inflammatory Agents><Anti-inflammatory><Antiinflammatories><Antiinflammatory Agents><Antiviral Agents><Antiviral Drugs><Antivirals><Assay><Bioassay><Biologic Assays><Biological Assay><COVID-19><COVID19><Cell Body><Cell fusion><Cells><Cholesterol><Communicable Diseases><Contracting Opportunities><Contracts><Coronaviridae><Coronavirus><Enzyme Gene><Enzymes><Epithelial Cells><Family suidae><Funding><Future><G24 protein><HCoV><Human><Hydroxylases><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><International><Investigation><Laboratories><Lead><Lipids><Lung><Lung Respiratory System><M mulatta><M. mulatta><Macaca mulatta><Membrane><Mice><Mice Mammals><Mixed Function Oxidases><Mixed Function Oxygenases><Modern Man><Monooxygenases><Murine><Mus><NIEHS><National Institute of Environmental Health Sciences><Organoids><PRRSV><Pathogenicity><Pb element><Pigs><Porcine respiratory and reproductive syndrome virus><Postdoc><Postdoctoral Fellow><Proteins><Publishing><Reporter><Research Associate><Respiratory Infections><Respiratory Tract Infections><Rhesus Macaque><Rhesus Monkey><SARS-CoV-2><SARS-CoV2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><Severe acute respiratory syndrome coronavirus 2><Suidae><Swine><Swine Infertility and Respiratory Syndrome Virus><Testing><Therapeutic><Toxic effect><Toxicities><Viral><Viral Diseases><Viral Vector><Virion><Virus><Virus Diseases><Virus Particle><Work><Wuhan coronavirus><ZIKV><Zika Virus><anti-viral agents><anti-viral drugs><anti-virals><antiinflammatory><beta lactam hydrolase><beta-Lactamase><beta-Lactamhydrolase><cholest-5-ene-3 beta,25-diol><corona virus><corona virus disease 2019><coronavirus disease 2019><global health emergency><heavy metal Pb><heavy metal lead><human CoV><human corona virus><human coronavirus><in vivo><innovate><innovation><innovative><membrane structure><porcine><post-doc><post-doctoral><pre-clinical safety><preclinical safety><pulmonary><suid><tool><viral infection><virus envelope><virus infection><virus-induced disease><zikav><β-Lactamase>