التفاصيل البيبلوغرافية
العنوان: |
Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms |
المؤلفون: |
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., 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, Correa Marrero, Miguel, id_orcid:0 000-0002-3840-3273, 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, 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., Nguyen, Phuong, Paulino, Joana, Pawar, Komal Ishwar, Peters, Jessica K., Pospiech, Thomas H., Safari, Maliheh, Sangwan, Smriti, Schaefer, Kaitlin, Thomas, Paul V., Thwin, Aye C., Trenker, Raphael, Tse, Eric, Tsui, Tsz Kin Martin, Wang, Feng, Whitis, Natalie, Yu, Zanlin, Zhang, Kaihua, Zhang, Yang, Zhou, Fengbo, Saltzberg, Daniel, QCRG Structural Biology Consortium, Hodder, Anthony J., Williams, Daniel M., White, Kris M., Rosales, Romel, Kehrer, Thomas, Miorin, Lisa, Moreno, Elena, Patel, Arvind H., Rihn, Suzannah, Khalid, Mir M., Vallejo-Gracia, Albert, Fozouni, Parinaz, Simoneau, Camille R., Roth, Theodore L., Wu, David, Karim, Mohd Anisul, Ghoussaini, Maya, Dunham, Ian, Berardi, Francesco, Weigang, Sebastian, Chazal, Maxime, Park, Jisoo, Logue, James, McGrath, Marisa, Weston, Stuart, Hastie, C. James, Elliott, Matthew, Brown, Fiona, Burness, Kerry A., Reid, Elaine, Dorward, Mark, Johnson, Clare, Wilkinson, Stuart G., Geyer, Anna, Giesel, Daniel M., Baillie, Carla, Raggett, Samantha, Leech, Hannah, Goodman, Nicola, Keough, Kathleen C., Lind, Abigail L., Zoonomia Consortium, Klesh, Reyna J., Hemphill, Kafi R., Carlson-Stevermer, Jared, Oki, Jennifer, Holden, Kevin, Maures, Travis, Pollard, Katherine S., Sali, Andrej, Agard, David A., Cheng, Yifan, Fraser, James S., Frost, Adam, Jura, Natalia, Kortemme, Tanja, Manglik, Aashish, Southworth, Daniel R., Stroud, Robert M., Alessi, Dario R., Davies, Paul, Frieman, Matthew B., Ideker, Trey, Abate, Carmen, Jouvenet, Nolwenn, Kochs, Georg, Shoichet, Brian, Ott, Melanie, Palmarini, Massimo, Shokat, Kevan M., García-Sastre, Adolfo, Rassen, Jeremy A., Grosse, Robert, Rosenberg, Oren S., Verba, Kliment A., Basler, Christopher F., Vignuzzi, Marco, Peden, Andrew A., Beltrao, Pedro, id_orcid:0 000-0002-2724-7703, Krogan, Nevan J. |
المصدر: |
Science, 370 (6521) |
بيانات النشر: |
AAAS |
سنة النشر: |
2020 |
المجموعة: |
ETH Zürich Research Collection |
الوصف: |
Introduction The emergence of three lethal coronaviruses in <20 years and the urgency of the COVID-19 pandemic have prompted efforts to develop new therapeutic strategies, including by repurposing existing agents. After performing a comparative analysis of the three pathogenic human coronaviruses severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1), SARS-CoV-2, and Middle East respiratory syndrome coronavirus (MERS-CoV), we identified shared biology and host-directed drug targets to prioritize therapeutics with potential for rapid deployment against current and future coronavirus outbreaks. Rationale Expanding on our recent SARS-CoV-2 interactome, we mapped the virus-host protein-protein interactions for SARS-CoV-1 and MERS-CoV and assessed the cellular localization of each viral protein across the three strains. We conducted two genetic screens of SARS-CoV-2 interactors to prioritize functionally-relevant host factors and structurally characterized one virus-host interaction. We then tested the clinical relevance of three more host factors by assessing risk in genetic cohorts or observing effectiveness of host factor–targeting drugs in real-world evidence. Results Quantitative comparison of the 389 interactors of SARS-CoV-2, 366 of SARS-CoV-1, and 296 of MERS-CoV highlighted interactions with host processes that are conserved across all three viruses, including where nonorthologous proteins from different virus strains seem to fill similar roles. We also localized each individually-expressed viral protein by microscopy and then raised and validated antisera against 14 SARS-CoV-2 proteins to determine their localization during infection. On the basis of two independent genetic perturbation screens, we identified 73 host factors that, when depleted, caused significant changes in SARS-CoV-2 replication. From this list of potential drug targets, we validated the biological and clinical relevance of Tom70, IL17RA, PGES-2, and SigmaR1. A 3-Å cryo–electron microscopy structure of Tom70, a mitochondrial ... |
نوع الوثيقة: |
article in journal/newspaper |
وصف الملف: |
application/application/pdf |
اللغة: |
English |
العلاقة: |
info:eu-repo/semantics/altIdentifier/wos/000596071300050; http://hdl.handle.net/20.500.11850/531946Test |
DOI: |
10.3929/ethz-b-000531946 |
الإتاحة: |
https://doi.org/20.500.11850/531946Test https://doi.org/10.3929/ethz-b-000531946Test https://doi.org/10.1126/science.abe9403Test https://hdl.handle.net/20.500.11850/531946Test |
حقوق: |
info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0Test/ ; Creative Commons Attribution 4.0 International |
رقم الانضمام: |
edsbas.B62400C8 |
قاعدة البيانات: |
BASE |