A SARS-CoV-2 protein interaction map reveals targets for drug repurposing
Date
2020-04-30Author
Gordon, David E.
Jang, Gwendolyn M.
Bouhaddou, Mehdi
Xu, Jiewei
Obernier, Kirsten
White, Kris M.
O’Meara, Matthew J.
Rezelj, Veronica V.
Guo, Jeffrey Z.
Swaney, Danielle L.
Tummino, Tia A.
Huettenhain, Ruth
Huettenhain, Ruth
Kaake, Robyn M.
Richards, Alicia L.
Tutuncuoglu, Beril
Foussard, Helene
Batra, Jyoti
Haas, Kelsey
Modak, Maya
Kim, Minkyu
Haas, Paige
Polacco, Benjamin J.
Braberg, Hannes
Fabius, Jacqueline M.
Eckhardt, Manon
Soucheray, Margaret
Bennett, Melanie J.
Cakir, Merve
McGregor, Michael J.
Li, Qiongyu
Meyer, Bjoern
Roesch, Ferdinand
Vallet, Thomas
Mac Kain, Alice
Miorin, Lisa
Moreno, Elena
Naing, Zun Zar Chi
Zhou, Yuan
Peng, Shiming
Shi, Ying
Zhang, Ziyang
Shen, Wenqi
Kirby, Ilsa T.
Melnyk, James E.
Chorba, John S.
Lou, Kevin
Dai, Shizhong A.
Barrio-Hernandez, Inigo
Memon, Danish
Hernandez-Armenta, Claudia
Lyu, Jiankun
Mathy, Christopher J.P.
Perica, Tina
Pilla, Kala B.
Ganesan, Sai J.
Saltzberg, Daniel J.
Rakesh, Ramachandran
Liu, Xi
Rosenthal, Sara B.
Calviello, Lorenzo
Venkataramanan, Srivats
Liboy-Lugo, Jose
Lin, Yizhu
Huang, Xi Ping
Liu, Yong Feng
Wankowicz, Stephanie A.
Bohn, Markus
Safari, Maliheh
Ugur, Fatima S.
Koh, Cassandra
Savar, Nastaran Sadat
Tran, Quang Dinh
Shengjuler, Djoshkun
Fletcher, Sabrina J.
O’Neal, Michael C.
Cai, Yiming
Chang, Jason C.J.
Broadhurst, David J.
Klippsten, Saker
Sharp, Phillip P.
Wenzell, Nicole A.
Kuzuoglu, Duygu
Wang, Hao Yuan
Trenker, Raphael
Young, Janet M.
Cavero, Devin A.
Hiatt, Joseph
Roth, Theodore L.
Rathore, Ujjwal
Subramanian, Advait
Noack, Julia
Hubert, Mathieu
Stroud, Robert M.
Frankel, Alan D.
Rosenberg, Oren S.
Verba, Kliment A.
Agard, David A.
Ott, Melanie
Emerman, Michael
Jura, Natalia
von Zastrow, Mark
Verdin, Eric
Ashworth, Alan
Schwartz, Olivier
d’Enfert, Christophe
Mukherjee, Shaeri
Jacobson, Matt
Malik, Harmit S.
Fujimori, Danica G.
Ideker, Trey
Craik, Charles S.
Floor, Stephen N.
Fraser, James S.
Gross, John D.
Sali, Andrej
Roth, Bryan L.
Ruggero, Davide
Taunton, Jack
Kortemme, Tanja
Beltrao, Pedro
Vignuzzi, Marco
García-Sastre, Adolfo
Shokat, Kevan M.
Shoichet, Brian K.
Krogan, Nevan J.
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A newly described coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 2019 (COVID-19), has infected over 2.3 million people, led to the death of more than 160,000 individuals and caused worldwide social and economic disruption1,2. There are no antiviral drugs with proven clinical efficacy for the treatment of COVID-19, nor are there any vaccines that prevent infection with SARS-CoV-2, and efforts to develop drugs and vaccines are hampered by the limited knowledge of the molecular details of how SARS-CoV-2 infects cells. Here we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins that physically associated with each of the SARS-CoV-2 proteins using affinity-purification mass spectrometry, identifying 332 high-confidence protein–protein interactions between SARS-CoV-2 and human proteins. Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (of which, 29 drugs are approved by the US Food and Drug Administration, 12 are in clinical trials and 28 are preclinical compounds). We screened a subset of these in multiple viral assays and found two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the sigma-1 and sigma-2 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.
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COVID-19Link to resource
https://www.nature.com/articles/s41586-020-2286-9Collections
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