Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms
Сравнительные сети взаимодействий белков хозяина и коронавирусов выявляют пан-вирусные механизмы заболевания
2020-10-15
SCID: 54.1/fh69efvq
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Tom70–ORF9b interactioncomparative viral-human protein interactioncryo-electron microscopy structural characterizationgenetic screening of host factorshost-coronavirus protein-protein interaction networks
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Abstract (AI)
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.
Key Findings
1
Comparative viral-human protein-protein interaction and viral protein localization analyses were performed for SARS-CoV-2, SARS-CoV-1, and MERS-CoV.
2
Functional genetic screens identified host factors that influence coronavirus proliferation, including mitochondrial chaperone Tom70.
3
Integration of genetically validated host factors with COVID-19 patient genetics and medical billing records revealed molecular mechanisms and potential drug treatments for further study.
4
Tom70 interacts with ORF9b from SARS-CoV-1 and SARS-CoV-2; this interaction was structurally characterized by cryo-electron microscopy.
Research Object
Comparative host–coronavirus protein–protein interaction networks for SARS-CoV-2, SARS-CoV-1, and MERS-CoV
Research Subject
Pan-viral molecular disease mechanisms and host factors revealed by comparative viral–human protein interactions, viral protein localization, functional genetic screens, structural characterization (Tom70–ORF9b), and integration with patient genetics and medical records to identify mechanisms and potential drug treatments
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2020-10-15
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