Article ; Online: Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms.
2020 Volume 370, Issue 6521
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 ...
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. |
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MeSH term(s) | COVID-19/metabolism ; Conserved Sequence ; Coronavirus Nucleocapsid Proteins/genetics ; Coronavirus Nucleocapsid Proteins/metabolism ; Cryoelectron Microscopy ; Host Microbial Interactions ; Humans ; Mitochondrial Membrane Transport Proteins/genetics ; Mitochondrial Membrane Transport Proteins/metabolism ; Mitochondrial Precursor Protein Import Complex Proteins ; Phosphoproteins/genetics ; Phosphoproteins/metabolism ; Protein Conformation ; Protein Interaction Maps ; Severe acute respiratory syndrome-related coronavirus/metabolism ; SARS-CoV-2/metabolism ; Severe Acute Respiratory Syndrome/metabolism |
Chemical Substances | Coronavirus Nucleocapsid Proteins ; Mitochondrial Membrane Transport Proteins ; Mitochondrial Precursor Protein Import Complex Proteins ; Phosphoproteins ; TOMM70 protein, human ; nucleocapsid phosphoprotein, SARS-CoV-2 |
Keywords | covid19 |
Language | English |
Publishing date | 2020-10-15 |
Publishing country | United States |
Document type | Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
ZDB-ID | 128410-1 |
ISSN | 1095-9203 ; 0036-8075 |
ISSN (online) | 1095-9203 |
ISSN | 0036-8075 |
DOI | 10.1126/science.abe9403 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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