Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms
David E. Gordon(Gladstone Institutes), Joseph Hiatt(Gladstone Institutes), Mehdi Bouhaddou(Gladstone Institutes), Veronica V. Rezelj(Centre National de la Recherche Scientifique), Svenja Ulferts(University of Freiburg), Hannes Braberg(Gladstone Institutes), Alexander S. Jureka(Georgia State University), Kirsten Obernier(Gladstone Institutes), Jeffrey Guo(Gladstone Institutes), Jyoti Batra(Gladstone Institutes), Robyn M. Kaake(Gladstone Institutes), Andrew R. Weckstein(Aetion (United States)), Tristan W. Owens(University of California System), Meghna Gupta(University of California System), Sergei Pourmal(University of California System), Erron W. Titus(University of California System), Merve Çakır(Gladstone Institutes), Margaret Soucheray(Gladstone Institutes), Michael McGregor(Gladstone Institutes), Zeynep Cakir(Gladstone Institutes), Gwendolyn Μ. Jang(Gladstone Institutes), Matthew J. O’Meara(University of Michigan), Tia A. Tummino(University of California, San Francisco), Ziyang Zhang(Howard Hughes Medical Institute), Helene Foussard(Gladstone Institutes), Ajda Rojc(Gladstone Institutes), Yuan Zhou(Gladstone Institutes), Dmitry Kuchenov(Gladstone Institutes), Ruth Hüttenhain(Gladstone Institutes), Jiewei Xu(Gladstone Institutes), Manon Eckhardt(Gladstone Institutes), Danielle L. Swaney(Gladstone Institutes), Jacqueline M. Fabius(University of California, San Francisco), Manisha R. Ummadi(Gladstone Institutes), Beril Tutuncuoglu(Gladstone Institutes), Ujjwal Rathore(Gladstone Institutes), Maya Modak(Gladstone Institutes), Paige Haas(Gladstone Institutes), Kelsey M. Haas(Gladstone Institutes), Zun Zar Chi Naing(Gladstone Institutes), Ernst H. Pulido(Gladstone Institutes), Ying Shi(Howard Hughes Medical Institute), Inigo Barrio‐Hernandez(European Bioinformatics Institute), Danish Memon(European Bioinformatics Institute), Eirini Petsalaki(European Bioinformatics Institute), Alistair S. Dunham(European Bioinformatics Institute), Miguel Correa Marrero(European Bioinformatics Institute), David F. Burke(European Bioinformatics Institute), Cassandra Koh(Centre National de la Recherche Scientifique), Thomas Vallet(Centre National de la Recherche Scientifique), Jesus A. Silvas(Georgia State University), Caleigh M. Azumaya(University of California System), Christian B. Billesbølle(University of California System), Axel F. Brilot(University of California System), Melody G. Campbell(University of California System), Amy Diallo(University of California System), Miles Sasha Dickinson(University of California System), Devan Diwanji(University of California System), Nadia Herrera(University of California System), Nick Hoppe(University of California System), Huong T. Kratochvil(University of California System), Yanxin Liu(University of California System), Gregory E. Merz(University of California System), Michelle Moritz(University of California System), Henry C. Nguyen(University of California System), Carlos Nowotny(University of California System), Cristina Puchades(University of California System), Alexandrea N. Rizo(University of California System), Ursula Schulze‐Gahmen(University of California System), Amber M. Smith(University of California System), Ming Sun(University of California System), I.D. Young(University of California System), Jianhua Zhao(University of California System), Daniel Asarnow(University of California System), J.T. Biel(University of California System), Alisa Bowen(University of California System), Julian R. Braxton(University of California System), Jen Chen(University of California System), Cynthia M. Chio(University of California System), Un Seng Chio(University of California System), Ishan Deshpande(University of California System), Loan Doan(University of California System), Bryan Faust(University of California System), Sebastián Flores(University of California System), Mingliang Jin(University of California System), Kate Kim(University of California System), Victor L. Lam(University of California System), Fei Li(University of California System), Junrui Li(University of California System), Yen-Li Li(University of California System), Yang Li(University of California System), Xi Liu(University of California System), Megan Lo(University of California System), Kyle E. Lopez(University of California System), Arthur A. Melo(University of California System), Frank R. Moss(University of California System), Phuong Nguyen(University of California System), Joana Paulino(University of California System), Komal Ishwar Pawar(University of California System), Jessica K. Peters(University of California System), Thomas H. Pospiech(University of California System), Maliheh Safari(University of California System), Smriti Sangwan(University of California System), Kaitlin Schaefer(University of California System), Paul V. Thomas(University of California System), Aye C. Thwin(University of California System), Raphael Trenker(University of California System), Eric Tse(University of California System), Tsz Kin Martin Tsui(University of California System), Feng Wang(University of California System), Natalie Whitis(University of California System), Zanlin Yu(University of California System), Kaihua Zhang(University of California System), Sunny Zhang(University of California System), Fengbo Zhou(University of California System), Daniel J. Saltzberg(University of California, San Francisco), Anthony J. Hodder(University of Sheffield), Amber S. Shun-Shion(University of Sheffield), Daniel M. Williams(University of Sheffield), Kris M. White(Icahn School of Medicine at Mount Sinai), Romel Rosales(Icahn School of Medicine at Mount Sinai), Thomas Kehrer(Icahn School of Medicine at Mount Sinai), Lisa Miorin(Icahn School of Medicine at Mount Sinai), Elena Moreno(Icahn School of Medicine at Mount Sinai), Arvind H. Patel(MRC University of Glasgow Centre for Virus Research), Suzannah J. Rihn(MRC University of Glasgow Centre for Virus Research), Mir M. Khalid(Gladstone Institutes), Albert Vallejo-Gracia(Gladstone Institutes), Parinaz Fozouni(Gladstone Institutes), Camille R. Simoneau(Gladstone Institutes), Theodore L. Roth(University of California, San Francisco), David Wu(University of California, San Francisco), Mohd Anisul Karim(Wellcome Sanger Institute), Maya Ghoussaini(Wellcome Sanger Institute), Ian Dunham(European Bioinformatics Institute), Francesco Berardi(University of Bari Aldo Moro), Sebastian Weigang(University of Freiburg), Maxime Chazal(Centre National de la Recherche Scientifique), Jisoo Park(University of California San Diego), James Logue(University of Maryland, Baltimore), Marisa E. McGrath(University of Maryland, Baltimore), Stuart Weston(University of Maryland, Baltimore), Robert Haupt(University of Maryland, Baltimore), C. James Hastie(University of Dundee), Matthew Elliott(University of Dundee), Fiona Brown(University of Dundee), Kerry Burness(University of Dundee), Elaine Reid(University of Dundee), Mark Dorward(University of Dundee), Clare Johnson(University of Dundee), Stuart G. Wilkinson(University of Dundee), Anna Geyer(University of Dundee), Daniel M. Giesel(University of Dundee), Carla Baillie(University of Dundee), Samantha Raggett(University of Dundee), Hannah Leech(University of Dundee), Rachel Toth(University of Dundee), Nicola Goodman(University of Dundee), Kathleen C. Keough(Gladstone Institutes), Abigail Lind(Gladstone Institutes), Reyna Klesh(Philadelphia Department of Public Health), Kafi Hemphill(University of California, San Francisco), Jared Carlson-Stevermer(Synthego (United States)), Jennifer Oki(Synthego (United States)), Kevin Holden(Synthego (United States)), Travis J. Maures(Synthego (United States)), Katherine S. Pollard(Gladstone Institutes), Andrej Šali(University of California, San Francisco), David A. Agard(University of California, San Francisco), Yifan Cheng(Howard Hughes Medical Institute), James S. Fraser(University of California, San Francisco), Adam Frost(University of California, San Francisco), Natalia Jura(University of California, San Francisco), Tanja Kortemme(University of California, San Francisco), Aashish Manglik(University of California, San Francisco), Daniel R. Southworth(University of California, San Francisco), Robert M. Stroud(University of California, San Francisco), Dario R. Alessi(University of Dundee), Paul Davies(University of Dundee), Matthew B. Frieman(University of Maryland, Baltimore), Trey Ideker(University of California San Diego), Carmen Abate(University of Bari Aldo Moro), Nolwenn Jouvenet(Centre National de la Recherche Scientifique), Georg Kochs(University of Freiburg), Brian K. Shoichet(University of California, San Francisco), Mélanie Ott(Gladstone Institutes), Massimo Palmarini(MRC University of Glasgow Centre for Virus Research), Kevan M. Shokat(Howard Hughes Medical Institute), Adolfo García‐Sastre(Tisch Hospital), Jeremy A. Rassen(Aetion (United States)), Robert Grosse(University of Freiburg), Oren S. Rosenberg(University of California, San Francisco), Kliment A. Verba(University of California, San Francisco), Christopher F. Basler(Georgia State University), Marco Vignuzzi(Centre National de la Recherche Scientifique), Andrew A. Peden(University of Sheffield), Pedro Beltrão(European Bioinformatics Institute), Nevan J. Krogan(Gladstone Institutes), Tristan W. Owens(University of California System), Meghna Gupta(University of California System), Sergei Pourmal(University of California System), Erron W. Titus(University of California System), Caleigh M. Azumaya(University of California System), Christian B. Billesbølle(University of California System), Axel F. Brilot(University of California System), Melody G. Campbell(University of California System), Amy Diallo(University of California System), Miles Sasha Dickinson(University of California System), Devan Diwanji(University of California System), Nadia Herrera(University of California System), Nick Hoppe(University of California System), Huong T. Kratochvil(University of California System), Yanxin Liu(University of California System), Gregory E. Merz(University of California System), Michelle Moritz(University of California System), Henry C. Nguyen(University of California System), Carlos Nowotny(University of California System), Cristina Puchades(University of California System), Alexandrea N. Rizo(University of California System), Ursula Schulze‐Gahmen(University of California System), Amber M. Smith(University of California System), Ming Sun(University of California System), I.D. Young(University of California System), Jianhua Zhao(University of California System), Daniel Asarnow(University of California System), J.T. Biel(University of California System), Alisa Bowen(University of California System), Julian R. Braxton(University of California System), Jen Chen(University of California System), Cynthia M. Chio(University of California System), Un Seng Chio(University of California System), Ishan Deshpande(University of California System), Loan Doan(University of California System), Bryan Faust(University of California System), Sebastián Flores(University of California System), Mingliang Jin(University of California System), Kate Kim(University of California System), Victor L. Lam(University of California System), Fei Li(University of California System), Junrui Li(University of California System), Yen-Li Li(University of California System), Yang Li(University of California System), Xi Liu(University of California System), Megan Lo(University of California System), Kyle E. Lopez(University of California System), Arthur A. Melo(University of California System), Frank R. Moss(University of California System), Phuong Nguyen(University of California System), Joana Paulino(University of California System), Komal Ishwar Pawar(University of California System), Jessica K. Peters(University of California System), Thomas H. Pospiech(University of California System), Maliheh Safari(University of California System), Smriti Sangwan(University of California System), Kaitlin Schaefer(University of California System), Paul V. Thomas(University of California System), Aye C. Thwin(University of California System), Raphael Trenker(University of California System), Eric Tse(University of California System), Tsz Kin Martin Tsui(University of California System), Feng Wang(University of California System), Natalie Whitis(University of California System), Zanlin Yu(University of California System), Kaihua Zhang(University of California System), Sunny Zhang(University of California System), Fengbo Zhou(University of California System), Donovan Trinidad, David A. Agard(University of California, San Francisco), Yifan Cheng(Howard Hughes Medical Institute), James S. Fraser(University of California, San Francisco), Adam Frost(University of California, San Francisco), Natalia Jura(University of California, San Francisco), Tanja Kortemme(University of California, San Francisco), Aashish Manglik(University of California, San Francisco), Daniel R. Southworth(University of California, San Francisco), Robert M. Stroud(University of California, San Francisco), Oren S. Rosenberg(University of California, San Francisco), Kliment A. Verba(University of California, San Francisco), Joana Damas(University of California System), Graham M. Hughes, Kathleen C. Keough(Gladstone Institutes), Corrie Painter, Nicole S. Persky, Marco Corbo(Centre National de la Recherche Scientifique), Bodgan Kirilenko, Michael Hiller(Gladstone Institutes), Klaus‐Peter Koepfli, Irene M. Kaplow, Morgan Wirthlin, Andreas R. Pfenning, Huabin Zhao(University of California System), Diane P. Genereux, Ross Swofford(University of Freiburg), Abigail Lind(Gladstone Institutes), Katherine S. Pollard(Gladstone Institutes), Oliver A. Ryderq, Martin Nweeia(University of California System), Jennifer R. S. Meadows(Synthego (United States)), Michael X. Dong(Gladstone Institutes), Ola Wallerman(University of Dundee), Vikki Marinescu, Kerstin Lindblad‐Toh, David A. Ray(Gladstone Institutes), Sarahjane Power, Emma C. Teeling, Gaurav Chauhan, Xue Li(University of California, San Francisco), Elinor K. Karlsson, Harris A. Lewin
Cited by 810Open Access
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.
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