Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms.
By D. Gordon, J. Hiatt, Mehdi Bouhaddou, V. Rezelj, Svenja Ulferts, Hannes Braberg, Alexander S. Jureka, K. Obernier, Jeffrey Z. Guo, Jyoti Batra and 188 more. 2020
659 citations recorded by the source corpus.
The COVID-19 (Coronavirus disease-2019) pandemic, caused by the SARS-CoV-2 coronavirus, is a significant 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 MERS-CoV. Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analysis 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-EM. Combining genetically-validated host factors with both COVID-19 patient genetic data and medical billing records identified important molecular mechanisms and potential drug treatments that merit further molecular and clinical study.
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- Ivan V. Anishchenko
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Citations in the corpus
- AlphaFold2 fails to predict protein fold switching (2022, background): “28 In two out of five cases, AlphaFold2 predicts a conformation similar to its β -sheet fold (TM-scores of (cid:1) 0.66 for both models).”
- The trRosetta server for fast and accurate protein structure prediction (2021, methodology): “…were shown to fi t well with the cryo-electron microscopy experimental data for these targets. trRosetta was also used to build structure models for severe acute respiratory syndrome coronavirus 2 – related proteins, such as NSP1 22 and ORF4a 23 , which do not have homologous structures in PDB.”
- Structure of SARS-CoV-2 ORF8, a rapidly evolving immune evasion protein (2020, background): “Within the lumen of the ER, SARS-CoV-2 ORF8 interacts with a variety of host proteins, including many factors involved in ER-associated degradation (13).”