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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 Weckstein,Tristan W. Owens,Meghna Gupta,Sergei Pourmal,Erron W. Titus,Merve Çakır,Margaret Soucheray,Michael McGregor,Zeynep Çakır,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,Iñigo Barrio-Hernandez,Danish Memon,Eirini Petsalaki,Alistair S. Dunham,Miguel 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,Sun Kyung Kim,Victor Lam,Fei Li,J Li,Yen-Li Li,Yang Li,Xi Liu,Megan Lo,Kyle E. Lopez,Arthur Melo,Frank R. Moss,Phuong T. Nguyen,Joana Paulino,Komal Ishwar Pawar,Jessica K. Peters,Thomas H. Pospiech,Maliheh Safari,Smriti Sangwan,Kaitlin Schaefer,Paul 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 L. 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,Melanie 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 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 Lam,Fēi Li,Junrui Li,Yen-Li Li,Yang Li,Xi Liu,Megan Lo,Kyle E. Lopez,Arthur Melo,Frank R. Moss,Phuong T. Nguyen,Joana Paulino,Komal Ishwar Pawar,Jessica K. Peters,Thomas H. Pospiech,Maliheh Safari,Smriti Sangwan,Kaitlin Schaefer,Paul Thomas,Aye C. Thwin,Raphael Trenker,Eric Tse,Tsz Kin Martin Tsui,Feng Wang,Natalie Whitis,Zanlin Yu,Kaihua Zhang,Zifeng Yang,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 A. 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,Shirley Xue Li,Elinor K. Karlsson,Harris A. Lewin

Coronavirus

Virology

Biology

2020

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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“Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms” is a paper by 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 Weckstein Tristan W. Owens Meghna Gupta Sergei Pourmal Erron W. Titus Merve Çakır Margaret Soucheray Michael McGregor Zeynep Çakır 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 Iñigo Barrio-Hernandez Danish Memon Eirini Petsalaki Alistair S. Dunham Miguel 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 Sun Kyung Kim Victor Lam Fei Li J Li Yen-Li Li Yang Li Xi Liu Megan Lo Kyle E. Lopez Arthur Melo Frank R. Moss Phuong T. Nguyen Joana Paulino Komal Ishwar Pawar Jessica K. Peters Thomas H. Pospiech Maliheh Safari Smriti Sangwan Kaitlin Schaefer Paul 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 L. 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 Melanie 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 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 Lam Fēi Li Junrui Li Yen-Li Li Yang Li Xi Liu Megan Lo Kyle E. Lopez Arthur Melo Frank R. Moss Phuong T. Nguyen Joana Paulino Komal Ishwar Pawar Jessica K. Peters Thomas H. Pospiech Maliheh Safari Smriti Sangwan Kaitlin Schaefer Paul Thomas Aye C. Thwin Raphael Trenker Eric Tse Tsz Kin Martin Tsui Feng Wang Natalie Whitis Zanlin Yu Kaihua Zhang Zifeng Yang 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 A. 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 Shirley Xue Li Elinor K. Karlsson Harris A. Lewin published in 2020. It has an Open Access status of “hybrid”. You can read and download a PDF Full Text of this paper here.