Document text
Principal Investigator: Ralph S Baric
Organization: UNIV OF NORTH CAROLINA CHAPEL HILL
Fiscal Year: 2020
Award: $766,414
Funding agency: National Institute of Allergy and Infectious Diseases
The 21st century has recorded the emergence of three highly pathogenic respiratory coronaviruses, including Severe Acute Respiratory Coronavirus (SARS-CoV) in 2003, the ongoing Middle East Respiratory Coronavirus (MERS-CoV) in 2013 and a novel SARS-like coronaviruses SARS-CoV2 (SARS2) in Wuhan, China in Dec 2019. SARS2 causes COVID19, a severe acute respiratory distress syndrome (ARDS) and has infected 95000 individuals with ~20% severe cases and a ~3% mortality rate, resulting in over 3700 deaths. In the elderly, mortality rates approach 15%. The overall program goals are to identify the viral and host determinants, which regulate the atomic-level interactions between the SARS2 S-glycoprotein and various ACE2 receptor and associated entry components such as cellular proteases. The impact of these studies are high, as these interactions regulate 2019-nHCoV species specificity and host tropism, which play critical roles in viral pathogenesis and inform the evolutionary pathways leading to virus emergence and spread in humans and perhaps other intermediate hosts. In parallel, we apply these and other findings to developing robust mouse models of SARS2-mediated human disease, which is critical for not only evaluating viral pathogenesis but also for future testing of antiviral drugs, immunotherapeutics and vaccines.
Terms: <2019 novel coronavirus><2019-nCoV><ARDS><Acute><Acute Respiratory Distress><Acute Respiratory Distress Syndrome><Adult ARDS><Adult RDS><Adult Respiratory Distress Syndrome><Animal Model><Animal Models and Related Studies><Animals><Antiviral Agents><Antiviral Drugs><Antivirals><Assay><Bats><Binding><Bioassay><Biochemical><Biologic Assays><Biological Assay><COVID-19><COVID19><CRISPR><CRISPR/Cas system><Cell Body><Cells><Cessation of life><China><Chiroptera><Cleaved cell><Clustered Regularly Interspaced Short Palindromic Repeats><CoV S protein><CoV emergence><CoV glycoprotein S><CoV spike glycoprotein><CoV spike protein><Collection><Coronaviridae><Coronavirus><Coronavirus glycoprotein S><Coronavirus spike protein><Country><Coupled><Crystallization><Da Nang Lung><Death><Development><Disasters><Disease><Disease Outbreaks><Disorder><Elderly><Electrons><Epidemic><Epithelial Cells><Esteroproteases><Foundations><Future><Generalized Growth><Genes><Genetic Alteration><Genetic Change><Genetic defect><Glycoproteins><Goals><Growth><Human><Immunotherapeutic agent><In Vitro><Individual><Infection><Investigators><Laboratories><Light><Lung><Lung Respiratory System><MERS corona virus><MERS coronavirus><MERS virus><MERS-CoV><Macromolecular Structure><Mainland China><Mammalia><Mammals><Mediating><Mice><Mice Mammals><Microscopic><Middle East><Middle East Respiratory Syndrome Corona Virus><Middle East Respiratory Syndrome Coronavirus><Middle East Respiratory Syndrome Virus><Middle East Respiratory Syndrome-CoV><Middle Eastern Respiratory Syndrome Corona virus><Middle Eastern Respiratory Syndrome Coronavirus><Middle Eastern Respiratory Syndrome Virus><Middle Eastern Respiratory Syndrome-CoV><Modern Man><Molecular><Molecular Configuration><Molecular Conformation><Molecular Interaction><Molecular Stereochemistry><Molecular Structure><Murine><Mus><Mutation><Negative Beta Particle><Negatrons><Outbreaks><Outcome><Pathogenesis><Pathogenicity><Pathway interactions><Peptidases><Peptide Hydrolases><Performance><Photoradiation><Physiologic><Physiological><Play><Position><Positioning Attribute><Protease Gene><Proteases><Proteinases><Proteins><Proteolytic Enzymes><Reagent><Receptor Protein><Research><Research Personnel><Researchers><Role><SARS><SARS Virus><SARS corona virus><SARS coronavirus><SARS coronavirus disease><SARS-Associated Coronavirus><SARS-CoV><SARS-CoV disease><SARS-CoV-2><SARS-CoV2><SARS-Related Coronavirus><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><Severe Acute Respiratory Syndrome><Severe Acute Respiratory Syndrome CoV disease><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><Severe Acute Respiratory Syndrome coronavirus disease><Severe acute respiratory syndrome coronavirus 2><Severities><Shock Lung><Site><Species Specificity><Stiff lung><Structure><Techniques><Testing><Tissue Growth><Tropism><Vaccines><Variant><Variation><Viral><Viral Pathogenesis><Virus><Virus Replication><Wuhan coronavirus><Zoonoses><Zoonotic><Zoonotic Infection><advanced age><airway epithelium><anti-viral agents><anti-viral drugs><anti-virals><cleaved><conformation><conformational state><corona virus><corona virus disease 2019><coronavirus S protein><coronavirus disease 2019><coronavirus emergence><coronavirus spike glycoprotein><cross-species spillover><cross-species transmission><developmental><elders><emergent CoV><emergent coronavirus><emerging CoV><emerging coronavirus><experience><genome mutation><geriatric><host jump><host switching><human disease><human model><human tissue><immune drugs><immune-based therapeutics><immunologic preparation><immunologic therapeutics><immunotherapeutics><immunotherapy agent><in vivo><insight><interspecies transmission><late life><later life><model of animal><model of human><model organism><mortality><mouse model><murine model><nCoV><new CoV><new coronavirus><novel><novel CoV><novel coronavirus><older adult><older person><ontogeny><pandemic><pandemic disease><pathway><prevent><preventing><programs><pulmonary><receptor><receptor binding><receptor bound><recombinant virus><respiratory><senior citizen><severe acute respiratory syndrome-CoV><social role><tissue tropism><transmission across species><transmission between species><transmitted across species><transmitted between species><transmitted cross-species><viral multiplication><viral replication><virus multiplication><virus pathogenesis><wet lung>