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

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

Science (New York, N.Y.) (2020-10-17)
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 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
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-74, ascites fluid
Sigma-Aldrich
IL-17A, recombinant, expressed in E. coli
Sigma-Aldrich
Tris(hydroxypropyl)phosphine, ≥80%
Sigma-Aldrich
Maltose solution, for molecular biology, BioReagent, ~20% in H2O
Sigma-Aldrich
Anti-β-Tubulin antibody, Mouse monoclonal, ~2.0 mg/mL, clone AA2, purified from hybridoma cell culture