1. Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms
- Author
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Gordon, David E, Hiatt, Joseph, Bouhaddou, Mehdi, Rezelj, Veronica V, Ulferts, Svenja, Braberg, Hannes, Jureka, Alexander S, Obernier, Kirsten, Guo, Jeffrey Z, Batra, Jyoti, Kaake, Robyn M, Weckstein, Andrew R, Owens, Tristan W, Gupta, Meghna, Pourmal, Sergei, Titus, Erron W, Cakir, Merve, Soucheray, Margaret, McGregor, Michael, Cakir, Zeynep, Jang, Gwendolyn, O’Meara, Matthew J, Tummino, Tia A, Zhang, Ziyang, Foussard, Helene, Rojc, Ajda, Zhou, Yuan, Kuchenov, Dmitry, Hüttenhain, Ruth, Xu, Jiewei, Eckhardt, Manon, Swaney, Danielle L, Fabius, Jacqueline M, Ummadi, Manisha, Tutuncuoglu, Beril, Rathore, Ujjwal, Modak, Maya, Haas, Paige, Haas, Kelsey M, Naing, Zun Zar Chi, Pulido, Ernst H, Shi, Ying, Barrio-Hernandez, Inigo, Memon, Danish, Petsalaki, Eirini, Dunham, Alistair, Marrero, Miguel Correa, Burke, David, Koh, Cassandra, Vallet, Thomas, Silvas, Jesus A, Azumaya, Caleigh M, Billesbølle, Christian, Brilot, Axel F, Campbell, Melody G, Diallo, Amy, Dickinson, Miles Sasha, Diwanji, Devan, Herrera, Nadia, Hoppe, Nick, Kratochvil, Huong T, Liu, Yanxin, Merz, Gregory E, Moritz, Michelle, Nguyen, Henry C, Nowotny, Carlos, Puchades, Cristina, Rizo, Alexandrea N, Schulze-Gahmen, Ursula, Smith, Amber M, Sun, Ming, Young, Iris D, Zhao, Jianhua, Asarnow, Daniel, Biel, Justin, Bowen, Alisa, Braxton, Julian R, Chen, Jen, Chio, Cynthia M, Chio, Un Seng, Deshpande, Ishan, Doan, Loan, Faust, Bryan, Flores, Sebastian, Jin, Mingliang, Kim, Kate, Lam, Victor L, Li, Fei, Li, Junrui, Li, Yen-Li, Li, Yang, Liu, Xi, Lo, Megan, Lopez, Kyle E, Melo, Arthur A, Moss, Frank R, Nguyen, Phuong, Paulino, Joana, Pawar, Komal Ishwar, and Peters, Jessica K
- Subjects
Biological Sciences ,Bioinformatics and Computational Biology ,Infectious Diseases ,Coronaviruses Therapeutics and Interventions ,Lung ,Coronaviruses ,Pneumonia ,Emerging Infectious Diseases ,Genetics ,Biodefense ,Pneumonia & Influenza ,Generic health relevance ,Infection ,Good Health and Well Being ,COVID-19 ,Conserved Sequence ,Coronavirus Nucleocapsid Proteins ,Cryoelectron Microscopy ,Host Microbial Interactions ,Humans ,Mitochondrial Membrane Transport Proteins ,Mitochondrial Precursor Protein Import Complex Proteins ,Phosphoproteins ,Protein Conformation ,Protein Interaction Maps ,Severe acute respiratory syndrome-related coronavirus ,SARS-CoV-2 ,Severe Acute Respiratory Syndrome ,QCRG Structural Biology Consortium ,Zoonomia Consortium ,General Science & Technology - 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.
- Published
- 2020