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 Guo, Jyoti Batra, Robyn M. Kaake, Andrew R. Weckstein, Tristan W. Owens, Meghna Gupta, Sergei Pourmal, Erron W. Titus, Merve Çakır, Margaret Soucheray, Michael McGregor, Zeynep Cakir, Gwendolyn Μ. 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 R. Ummadi, Beril Tutuncuoglu, Ujjwal Rathore, Maya Modak, Paige Haas, Kelsey M. Haas, Zun Zar Chi Naing, Ernst H. Pulido, Ying Shi, Inigo Barrio‐Hernandez, Danish Memon, Eirini Petsalaki, Alistair S. Dunham, Miguel Correa Marrero, David F. Burke, Cassandra Koh, Thomas Vallet, Jesus A. Silvas, Caleigh M. Azumaya, Christian B. Billesbølle, Axel F. Brilot, Melody G. Campbell, Amy Diallo, Miles Sasha Dickinson, Devan Diwanji, Nadia Herrera, Nick Hoppe, Huong T. Kratochvil, Yanxin Liu, Gregory E. Merz, Michelle Moritz, Henry C. Nguyen, Carlos Nowotny, Cristina Puchades, Alexandrea N. Rizo, Ursula Schulze‐Gahmen, Amber M. Smith, Ming Sun, I.D. Young, Jianhua Zhao, Daniel Asarnow, J.T. Biel, Alisa Bowen, Julian R. Braxton, Jen Chen, Cynthia M. Chio, Un Seng Chio, Ishan Deshpande, Loan Doan, Bryan Faust, Sebastián Flores, Mingliang Jin, Kate Kim, Victor L. Lam, Fei Li, Junrui Li, Yen-Li Li, Yang Li, Xi Liu, Megan Lo, Kyle E. Lopez, Arthur A. Melo, Frank R. Moss, Phuong Nguyen, Joana Paulino, Komal Ishwar Pawar, Jessica K. Peters
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.