Document text
Principal Investigator: eric freed
Organization: DIVISION OF BASIC SCIENCES - NCI
Fiscal Year: 2022
Award: $247,114
Funding agency: National Cancer Institute
In a structural and functional analysis of the SARS-CoV-2 S protein that we recently started, we have determined that MARCH8, but not a catalytically inactive MARCH8 mutant, targets the S proteins of SARS-CoV, MERS-CoV, and SARS-CoV-2 for degradation. We also showed that human airway epithelial cells express MARCH8 upon treatment with IFN. The work on MARCH protein-mediated antagonism may reveal new opportunities for therapeutic intervention with S protein trafficking and incorporation into virus particles. This work was recently published (mBio 12: e00219-21, 2021). _____In a separate study, we showed that virion incorporation of PSGL-1 on SARS-CoV and SARS-CoV-2 pseudovirions blocks S protein-mediated virus attachment and infection of target cells. These results demonstrate that PSGL-1 can serve as an IFN-regulated host factor that restricts CoV infectivity. This work was recently published (Viruses 13: 46, 2020). _____We are now focusing on defining the mechanism by which MARCH E3 ubiquitin ligases antagonize the SARS-CoV-2 S protein, evaluating the antiviral activity of GBP ATPases against the SARS-CoV-2 S protein, and measuring the expression of host cell anti-SARS-CoV-2 S protein antagonists in relevant cell types.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><AIDS Virus><ATP phosphohydrolase><ATPase><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Address><Adenosine Triphosphatase><Adenosinetriphosphatase><Binding><Binding Proteins><Biogenesis><Body Tissues><CD162 antigen><CD62E Antigens><CD62L Antigens><CD62P Antigens><COVID-19 virus><COVID19 virus><Cell Adhesion Molecule E-Selectin><Cell Body><Cell Locomotion><Cell Migration><Cell Movement><Cell Surface Glycoproteins><Cell Surface Receptors><Cells><Cellular Membrane><Cellular Migration><Cellular Motility><CoV S protein><CoV glycoprotein S><CoV spike glycoprotein><CoV spike protein><CoV-2><CoV2><Collaborations><Coronaviridae><Coronavirus><Coronavirus glycoprotein S><Coronavirus spike protein><Cryo-electron tomography><Development><E-Selectin><E3 Ligase><E3 Ubiquitin Ligase><ELAM-1><Endothelial Adhesion Molecule 1><Endothelial Cells><Endothelial Leukocyte Adhesion Molecule-1><Epithelial Cells><Family><GMP-140><Gamma interferon><Genes><Goals><HIV><HIV envelope protein><HIV-1><HIV-I><HIV1><Host Factor><Host Factor Protein><Human><Human Immunodeficiency Virus Type 1><Human Immunodeficiency Viruses><Human immunodeficiency virus 1><IFN><IFN-Gamma><IFN-g><IFN-γ><IFNG><IFNγ><Immune><Immune Interferon><Immune response><Immunes><Immunological response><Infection><Innate Immune Response><Innate Immunity><Integration Host Factors><Interferon Gamma><Interferon Type II><Interferon-gamma><Interferons><L-Selectin><LAM-1><LAM-1 Leukocyte Adhesion Molecule><LAV-HTLV-III><LECAM-1><LECAM-2><LECAM-3><Leu-8 Antigen><Leukocyte Endothelial Cell Adhesion Molecule 2><Ligand Binding Protein><Ligand Binding Protein Gene><Lymphadenopathy-Associated Virus><Lymphocyte Adhesion Molecule 1><MERS corona virus><MERS coronavirus><MERS virus><MERS-CoV><Measures><Mediating><Mel-14 Antigen><Membrane><Membrane Glycoproteins><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 Interaction><Motility><NIEHS><National Institute of Environmental Health Sciences><Native Immunity><Natural Immunity><Non-Specific Immunity><Nonspecific Immunity><Origin of Life><P-Selectin><P-selectin glycoprotein ligand-1><P-selectin ligand protein><PSGL-1><Peptide Domain><Platelet alpha-Granule Membrane Protein><Play><Protein Binding><Protein Domains><Protein Trafficking><Proteins><Publishing><Respiratory Epithelium><Role><SARS Virus><SARS corona virus><SARS corona virus 2><SARS coronavirus><SARS-Associated Coronavirus><SARS-CO-V2><SARS-COVID-2><SARS-CoV><SARS-CoV-1><SARS-CoV-2><SARS-CoV2><SARS-Related Coronavirus><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Severe Acute Respiratory Coronavirus><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome related corona virus 2><Structure><Structure of respiratory epithelium><Surface><Surface Glycoproteins><TQ1 Antigen><Tertiary Protein Structure><Therapeutic Intervention><Tissues><Ubiquitin Protein Ligase><Ubiquitin-Protein Ligase Complexes><Ubiquitin-Protein Ligase E3><Vaccine Design><Vaccines><Viral><Viral Diseases><Virion><Virus><Virus Diseases><Virus Particle><Virus Replication><Virus-HIV><Virus-like particle><Work><Wuhan coronavirus><adaptive immunity><airway epithelium><antagonist><anti-viral development><anti-viral drug development><anti-viral therapeutic development><anti-viral therapy development><antiviral development><antiviral drug development><antiviral therapeutic development><antiviral therapy development><block viral entry><bound protein><cell motility><cell type><corona virus><coronavirus S protein><coronavirus disease 2019 virus><coronavirus disease-19 virus><coronavirus spike glycoprotein><cryo-EM tomography><cryoEM tomography><cryoelectron tomography><developing anti-viral agent><developing anti-viral drug><developing anti-viral therapeutic><developing anti-viral therapy><developing antiviral agent><developing antiviral drug><developing antiviral therapeutic><developing antiviral therapy><developmental><electron cryo-tomography><endothelial leukocyte adhesion molecule><experience><guanylate><hCoV19><host response><immune system response><immunoresponse><inhibit viral entry><insight><intervention therapy><lFN-Gamma><membrane structure><mutant><nCoV2><neutralizing antibody><particle><protein transport><severe acute respiratory syndrome-CoV><social role><trafficking><ubiquitin-protein ligase><viral entry blocker><viral entry inhibitor><viral infection><viral multiplication><viral replication><viral transmission><virus infection><virus multiplication><virus transmission><virus-induced disease><virus-like nanoparticles><viruslike particle>