Accès ouvert déclaré
2020
article
A SARS-CoV-2 protein interaction map reveals targets for drug repurposing
Christoper Mathy, Robert M. Stroud, Kevin Lou, Jiewei Xu, Charles S. Craik, Jason C. Chang, Marco Vignuzzi, Andrej Šali, Pedro Beltrão, Joseph Hiatt, Shiming Peng, Kelsey M. Haas, Duygu Kuzuoglu, Fatima S. Ugur, Eric Verdin, Nevan J. Krogan, Danica Galonić Fujimori, Tanja Kortemme, Ramachandran Rakesh, Michael McGregor, Kirsten Obernier, José Liboy-Lugo, Yizhu Lin, Natalia Jura, Jack Taunton, Ruth Hüttenhain, John S. Chorba, Wenqi Shen, John D. Gross, Michael Emerman, Mathieu Hubert, David A. Agard, Merve Çakır, Yongfeng Liu, Shizhong Dai, Hannes Braberg, Lorenzo Calviello, Jacqueline M. Fabius, Robyn M. Kaake, Benjamin J. Polacco, Alice Mac Kain, Kevan M. Shokat, Veronica V. Rezelj, Devin A. Cavero, Stephanie A. Wankowicz, Margaret Soucheray, Saker Klippsten, Janet M. Young, Alan Ashworth, Oren S. Rosenberg, Alan D. Frankel, Jiankun Lyu, Gwendolyn Μ. Jang, Matthew J. O’Meara, Daniel J. Salzberg, Lisa Miorin, Manon Eckhardt, Olivier Schwartz, Ujjwal Rathore, Nastaran Sadat Savar, Inigo Barrio‐Hernandez, Bryan L. Roth, Julia Noack, Kliment A. Verba, David Broadhurst, Danielle L. Swaney, Markus‐Frederik Bohn, Alicia Richards, Stephen N. Floor, David E. Gordon, Theodore L. Roth, Ilsa T. Kirby, Tia A. Tummino, Sai J. Ganesan, Jyoti Batra, James E. Melnyk, Minkyu Kim, Maya Modak, James S. Fraser, Ying Shi, Cassandra Koh, Yuan Zhou, Nicole A. Wenzell, Matt Jacobsen, Kris M. White, Shaeri Mukherjee, Davide Ruggero, yiming Cai, Tina Perica, Zun Zar Naig, Claudia Hernández-Armenta, Sara Brin Rosenthal, Hao‐Yuan Wang, Ziyang Zhang, Melanie J. Bennett, Michael Oneal, Maliheh Safari, Xi Liu, Brian K. Shoichet, Paige Haas, Jeffrey Z. Gou, Sabrina Johanna Fletcher, Adavait Subramanian, Thomas Vallet, Raphael Trenker, Kala Bharath Pilla, Djoshkun Shengjuler, Mark von Zastrow, Xi‐Ping Huang, Phillip P. Sharp, Bjoern Meyer, Harmit S. Malik, Beril Tutuncuoglu, Mehdi Bouhaddou, Adolfo García‐Sastre, Christophe d’Enfert, Qiongyu Li, Ferdinand Roesch, Helene Foussard, Mélanie Ott, Danish Memon, Trey Ideker, Quang Tran, Srivats Venkataramanan
3Citations signalées, ce qui n’est pas une note de qualité
1Institutions déclarées
1Pays d’affiliation déclarés
Rattachement africain : us.
Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
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Les sujets associés
Computational Drug Discovery Methods