Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms
Open Access
- 4 December 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 370 (6521), 1181-+
- https://doi.org/10.1126/science.abe9403
Abstract
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 characterized using cryo–electron microscopy. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified molecular mechanisms and potential drug treatments that merit further molecular and clinical study.Funding Information
- National Science Foundation (1650113)
- National Institutes of Health (P01AI063302, P50AI150476, R01AI120694, R01AI122747, R01AI143292, U19AI135972, U19AI135990)
- National Institutes of Health (P01AI120943, R01AI143292)
- National Institutes of Health (U19AI135990)
- National Institutes of Health (R35GM122481)
- National Institutes of Health (U19AI135972)
- National Institute of Allergy and Infectious Diseases (R01AI128214)
- National Human Genome Research Institute (R01 HG009979)
- National Institutes of Health (K99GM138753)
- Howard Hughes Medical Institute (None)
- National Institutes of Health (T32GM007618)
- NIH Office of the Director (AI150476)
- U.S. Department of Defense (W81XWH-20-1-0270)
- National Institute of General Medical Sciences (F32GM137463)
- National Institutes of Health (F32CA239333)
- National Institutes of Health (F32 CA239336)
- National Institutes of Health (T32GM007618)
- National Institutes of Health (F30AI143401)
- Chan Zuckerberg Initiative
- LABoratoires d’EXcellence ARCANE
- Biomedical Advanced Research and Development Authority (ASPR-20-01495)
- Bill and Melinda Gates Foundation (INV-006099)
- Defense Advanced Research Projects Agency (HR0011-20-2-0040)
- Defense Sciences Office, DARPA (HR0011-19-2-0020)
- Fast Grants (COVID19 grant)
- Medical Research Council (MC PC 19026)
- Defense Sciences Office, DARPA (HR0011-19-2-0020)
- Medical Research Council (MC_UU_12016/2)
- Defense Sciences Office, DARPA (HR0011-19-2-0020)
- Defense Sciences Office, DARPA (HR0011-19-2-0020)
- Hoffman-La Roche
- Fast Grants (COVID19 grant)
- Gladstone Institutes
- Roddenberry Foundation
- Defense Sciences Office, DARPA (HR0011-19-2-0020)
- National Institute of Neurological Disorders and Stroke (R01 NS089713)
- Open Philanthropy Project
- JPB Foundation
- National Institute of Allergy and Infectious Diseases (HHSN272201400008C)
- Defense Sciences Office, DARPA (HR0011-19-2-0020)
- Damon Runyon Cancer Research Foundation (DRG-2402-20)
- Burroughs Wellcome Fund (1019894)
- Laboratory for Genomics Research (Excellence in Research Award COVID19)
- URGENCE COVID-19 Institut Pasteur fundraising campaign
- FastGrants (COVID19 grant)
- The Augusta University-Georgia State University Seed Grant
- Medical Research Council (MC_UU_12016/2)
- Vir Biotechnology
- The Ron Conway Family
- The Laboratory for Genomics Research (Excellence in Research Award, 133122P)
- DFG under Germany’s Excellence Strategy (EXC-2189, project ID 390939984)
- Chan Zuckerberg Biohub (None)
- NIGMS (R01 GM24485)
- Laboratory for Genomics Research (Excellence in Research Award)
- URGENCE COVID-19 Institut Pasteur fundraising campaign
- BBSRC (BB/S009566/1, BB/L002841/1)
- BBSRC (BB/S009566/1, BB/L002841/1)
- Biotechnology and Biological Sciences Research Council (BB/J014443/1)
- The Laboratory for Genomics Research (Excellence in Research Award, 133122P)
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