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

Authors: 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, Thomas H. Pospiech, Maliheh Safari, Smriti Sangwan, Kaitlin Schaefer, Paul V. Thomas, Aye C. Thwin, Raphael Trenker, Eric Tse, Tsz Kin Martin Tsui, Feng Wang, Natalie Whitis, Zanlin Yu, Kaihua Zhang, Sunny Zhang, Fengbo Zhou, Daniel J. Saltzberg, Anthony J. Hodder, Amber S. Shun-Shion, Daniel M. Williams, Kris M. White, Romel Rosales, Thomas Kehrer, Lisa Miorin, Elena Moreno, Arvind H. Patel, Suzannah J. Rihn, Mir M. Khalid, Albert Vallejo-Gracia, Parinaz Fozouni, Camille R. Simoneau, Theodore L. Roth, David Wu, Mohd Anisul Karim, Maya Ghoussaini, Ian Dunham, Francesco Berardi, Sebastian Weigang, Maxime Chazal, Jisoo Park, James Logue, Marisa E. McGrath, Stuart Weston, Robert Haupt, C. James Hastie, Matthew Elliott, Fiona Brown, Kerry Burness, Elaine Reid, Mark Dorward, Clare Johnson, Stuart G. Wilkinson, Anna Geyer, Daniel M. Giesel, Carla Baillie, Samantha Raggett, Hannah Leech, Rachel Toth, Nicola Goodman, Kathleen C. Keough, Abigail Lind, Reyna Klesh, Kafi Hemphill, Jared Carlson-Stevermer, Jennifer Oki, Kevin Holden, Travis J. Maures, Katherine S. Pollard, Andrej Šali, David A. Agard, Yifan Cheng, James S. Fraser, Adam Frost, Natalia Jura, Tanja Kortemme, Aashish Manglik, Daniel R. Southworth, Robert M. Stroud, Dario R. Alessi, Paul Davies, Matthew B. Frieman, Trey Ideker, Carmen Abate, Nolwenn Jouvenet, Georg Kochs, Brian K. Shoichet, Mélanie Ott, Massimo Palmarini, Kevan M. Shokat, Adolfo García‐Sastre, Jeremy A. Rassen, Robert Grosse, Oren S. Rosenberg, Kliment A. Verba, Christopher F. Basler, Marco Vignuzzi, Andrew A. Peden, Pedro Beltrão, Nevan J. Krogan, Tristan W. Owens, Meghna Gupta, Sergei Pourmal, Erron W. Titus, 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, Thomas H. Pospiech, Maliheh Safari, Smriti Sangwan, Kaitlin Schaefer, Paul V. Thomas, Aye C. Thwin, Raphael Trenker, Eric Tse, Tsz Kin Martin Tsui, Feng Wang, Natalie Whitis, Zanlin Yu, Kaihua Zhang, Sunny Zhang, Fengbo Zhou, Donovan Trinidad, David A. Agard, Yifan Cheng, James S. Fraser, Adam Frost, Natalia Jura, Tanja Kortemme, Aashish Manglik, Daniel R. Southworth, Robert M. Stroud, Oren S. Rosenberg, Kliment A. Verba, Joana Damas, Graham M. Hughes, Kathleen C. Keough, Corrie Painter, Nicole S. Persky, Marco Corbo, Bodgan Kirilenko, Michael Hiller, Klaus‐Peter Koepfli, Irene M. Kaplow, Morgan Wirthlin, Andreas R. Pfenning, Huabin Zhao, Diane P. Genereux, Ross Swofford, Abigail Lind, Katherine S. Pollard, Oliver A. Ryderq, Martin Nweeia, Jennifer R. S. Meadows, Michael X. Dong, Ola Wallerman, Vikki Marinescu, Kerstin Lindblad‐Toh, David A. Ray, Sarahjane Power, Emma C. Teeling, Gaurav Chauhan, Xue Li, Elinor K. Karlsson, Harris A. Lewin - Science 2020 cited by 819

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.