期刊
SCIENCE
卷 370, 期 6521, 页码 1181-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abe9403
关键词
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资金
- National Institutes of Health (NIH) [P01AI063302, P50AI150476, R01AI120694, R01AI122747, R01AI143292, U19AI135972, U19AI135990, P01AI120943, U19 AI135990]
- National Institute of Allergy and Infectious Diseases (NIAID) [R01AI128214]
- National Institute of Neurological Disorders and Stroke [R01 NS089713]
- NIH Office of the Director [AI150476]
- NIGMS [R01 GM24485, R35GM122481]
- Fast Grant for COVID-19 from the Emergent Ventures program at the Mercatus Center of George Mason University
- Roddenberry Foundation Gladstone Institutes
- Defense Advanced Research Projects Agency [HR0011-19-2-0020, HR0011-20-2-0040]
- Fast Grant for COVID-19
- CRIP (Center for Research for Influenza Pathogenesis), a NIAID [HHSN272201400008C]
- NIAID [U19AI135972]
- DoD [W81XWH-20-1-0270]
- Bill and Melinda Gates Foundation [INV-006099]
- BARDA [ASPR-20-01495]
- Howard Hughes Medical Institute
- Damon Runyon Cancer Research Foundation [DRG-240220]
- Burroughs Wellcome Fund [1019894]
- Chan Zuckerberg Initiative
- Cytoscape: A modeling platform for biomolecular networks [NHGRI R01 HG009979]
- JPB Foundation
- Open Philanthropy Project [2020-215611 (5384)]
- Laboratoire d'Excellence [ANR-10-LABX-62-IBEID]
- URGENCE COVID-19 Institut Pasteur fundraising campaign
- BBSRC [BB/S009566/1, BB/L002841/1]
- BBSRC White Rose DTP [BB/J014443/1]
- Augusta University-Georgia State University Seed Grant program
- MRC [MC PC 19026, MC_UU_12016/2]
- Medical Research Council [MC_UU_12016/2]
- DFG under Germany's Excellence Strategy [EXC-2189, 390939984]
- F. Hoffmann-La Roche
- Vir Biotechnology
- UCSF Medical Scientist Training Program [T32GM007618]
- NIH-NIAID [F30AI143401]
- NCI at NIH [F32CA239333]
- NIH [K99GM138753, F32 CA239336]
- National Science Foundation [1650113]
- National Institute of General Medical Sciences [F32GM137463]
- Quantitative Biosciences Institute
- Defense Advance Research Projects Agency [HR0011-19-2-0020]
- Laboratory For Genomics Research
- FastGrants COVID-19 grant
- BBSRC [1945669, BB/S009566/1] Funding Source: UKRI
- MRC [MC_UU_00018/1, MR/V03541X/1, MC_PC_19026, MC_UU_12016/2, MC_UU_12014/2] Funding Source: UKRI
- Bill and Melinda Gates Foundation [INV-006099] Funding Source: Bill and Melinda Gates Foundation
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.
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