Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 ORF9b, an interaction we structurally…

• NS
  National Science Foundation

  Awards: T32GM007618, 1650113, 1019894
• UD
  U.S. Department of Defense

  Awards: W81XWH-20-1-0270, W81XWH
• HH
  Howard Hughes Medical Institute
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  Burroughs Wellcome Fund

  Award: 1019894
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  Bill and Melinda Gates Foundation

  Award: INV-006099
• DR
  Damon Runyon Cancer Research Foundation

  Award: DRG-2402-20
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  George Mason University
• FH
  F. Hoffmann-La Roche
• IS
  Icahn School of Medicine at Mount Sinai
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  JPB Foundation
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  Gladstone Institutes
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  Georgia State University
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  Roddenberry Foundation
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  Augusta University
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  LABoratoires d’EXcellence ARCANE
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  Open Philanthropy Project

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  Chan Zuckerberg Initiative
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  Fast Grants

  Award: COVID19 grant
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  Vir Biotechnology
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  Deutsche Forschungsgemeinschaft

  Awards: 390939984, EXC-2189, ANR-10-LABX-62-IBEID
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  Agence Nationale de la Recherche

  Awards: 10-LABX-62-IBEID, ANR-10-LABX-62-IBEID, ANR-10, ANR-10-LABX-62
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  National Institutes of Health

  Awards: R01 HG009979, U19 AI135990, P01AI063302, AI150476, P01AI120943, R01AI120694, F32 CA239336, GM24485, F30AI143401, F32CA239333, P01AI120943, R01AI143292, T32GM007618, R35GM122481, U19AI135972, COVID-19, P01AI063302, P50AI150476, R01AI120694, R01AI122747, R01AI143292, U19AI135972, U19AI135990, W81XWH, R01AI122747, K99GM138753, HHSN272201400008C, ASPR-20-01495, P50AI150476, R01AI143292, U19AI135990
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  Defense Advanced Research Projects Agency

  Award: HR0011-20-2-0040
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  University of California, San Francisco

  Award: T32GM007618
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  Advanced Research Projects Agency
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  Biomedical Advanced Research and Development Authority

  Award: ASPR-20-01495
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  Medical Research Council

  Awards: MC PC 19026, MC_PC_19026, MC_UU_00018/1, MC_UU_12016, MC_UU_12016/2, COVID-19
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  Biotechnology and Biological Sciences Research Council

  Awards: BB/L002841/1, BB/J014443/1, BB/S009566/1, S009566, BB/S009566/1, 1945669, BB/S009566/1, BB/L002841/1, BB/L002841/1, BB/J014443
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  National Human Genome Research Institute

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  NIH Office of the Director

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  National Cancer Institute
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  National Institute of General Medical Sciences

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  National Institute of Allergy and Infectious Diseases

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  National Institute of Neurological Disorders and Stroke

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  Defense Sciences Office, DARPA

  Award: HR0011-19-2-0020