Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms
- PMID:33060197
- PMCID: PMC7808408
- DOI: 10.1126/science.abe9403
Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms
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.
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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Comment in
- Conserved host-pathogen interactions identify novel treatment options in betacoronavirus infections.Lukassen S, Eils R.Lukassen S, et al.Signal Transduct Target Ther. 2021 Feb 10;6(1):57. doi: 10.1038/s41392-021-00480-z.Signal Transduct Target Ther. 2021.PMID:33563888Free PMC article.No abstract available.
- Olanzapine, risperidone and quetiapine: Do these atypical antipsychotics have a protective effect for SARS-CoV-2?Prokopez CR, Farinola R, Vallejos M, Lopredo LS, Sfriso LE, Chiapella LC, Arce C, Corral RM, Cuesta MJ, Alomo M.Prokopez CR, et al.Schizophr Res. 2022 Mar;241:140-141. doi: 10.1016/j.schres.2022.01.035. Epub 2022 Jan 24.Schizophr Res. 2022.PMID:35123336Free PMC article.No abstract available.
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