Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms

, David E Gordon, Joseph Hiatt, Mehdi Bouhaddou, Veronica V Rezelj, Svenja Ulferts, Hannes Braberg, Alexander S Jureka, Kirsten Obernier, Jeffrey Z Guo, Jyoti Batra, Robyn M Kaake, Andrew R Weckstein, Tristan W Owens, Meghna Gupta, Sergei Pourmal, Erron W Titus, Merve Cakir, Margaret Soucheray, Michael McGregorZeynep Cakir, Gwendolyn Jang, Matthew J O'Meara, Tia A Tummino, Ziyang Zhang, Helene Foussard, Ajda Rojc, Yuan Zhou, Dmitry Kuchenov, Ruth Hüttenhain, Jiewei Xu, Manon Eckhardt, Danielle L Swaney, Jacqueline M Fabius, Manisha Ummadi, Beril Tutuncuoglu, Ujjwal Rathore, Maya Modak, Paige Haas, Kelsey M Haas, Daniel M Williams, C James Hastie, Matthew Elliott, Fiona Brown, Kerry A Burness, Elaine Reid, Carla Baillie, Samantha Raggett, Rachel Toth, Dario R Alessi, Paul Davies, Adolfo García-Sastre, Jeremy A. Rassen, Robert Grosse, Oren S. Rosenberg, Kliment A. Verba, Christopher F. Basler, Marco Vignuzzi, Andrew A. Peden, Pedro Beltrao, Nevan J. Krogan

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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.

Original languageEnglish
Article numbereabe9403
Number of pages39
JournalScience (New York, N.Y.)
Early online date15 Oct 2020
Publication statusE-pub ahead of print - 15 Oct 2020

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