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TitleComparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms.
Journal, issue, pagesScience, Vol. 370, Issue 6521, Year 2020
Publish dateDec 4, 2020
AuthorsDavid 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 McGregor / Zeynep 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 / Zun Zar Chi Naing / Ernst H Pulido / Ying Shi / Inigo Barrio-Hernandez / Danish Memon / Eirini Petsalaki / Alistair Dunham / Miguel Correa Marrero / David Burke / Cassandra Koh / Thomas Vallet / Jesus A Silvas / Caleigh M Azumaya / Christian 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 / Iris D Young / Jianhua Zhao / Daniel Asarnow / Justin Biel / Alisa Bowen / Julian R Braxton / Jen Chen / Cynthia M Chio / Un Seng Chio / Ishan Deshpande / Loan Doan / Bryan Faust / Sebastian 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 / Yang Zhang / Fengbo Zhou / Daniel 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 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 McGrath / Stuart Weston / Robert Haupt / C James Hastie / Matthew Elliott / Fiona Brown / Kerry A 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 L Lind / / Reyna J Klesh / Kafi R Hemphill / Jared Carlson-Stevermer / Jennifer Oki / Kevin Holden / Travis Maures / Katherine S Pollard / Andrej Sali / 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 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 Beltrao / Nevan J Krogan /
PubMed AbstractThe 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 ...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.
External linksScience / PubMed:33060197 / PubMed Central
MethodsEM (single particle)
Resolution3.05 Å
Structure data

EMDB-22829, PDB-7kdt:
Human Tom70 in complex with SARS CoV2 Orf9b
Method: EM (single particle) / Resolution: 3.05 Å

Source
  • homo sapiens (human)
  • severe acute respiratory syndrome coronavirus 2
KeywordsVIRAL PROTEIN / Orf9b / Tom70 / mitochondria / virus infection / SARS CoV2

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