A SARS-CoV-2 protein interaction map reveals targets for drug repurposing
Creators: name: Mathy, Christoper J.P.
name: Stroud, Robert M.
name: Lou, Kevin
name: Xu, Jiewei
name: Craik, Charles S.
name: Chang, Jason C.J.
name: Vignuzzi, Marco
name: Sali, Andrej
name: Beltrao, Pedro
name: Hiatt, Joseph
name: Peng, Shiming
name: Haas, Kelsey
name: Kuzuoglu, Duygu
name: Ugur, Fatima S.
name: Verdin, Eric
name: Krogan, Nevan J.
name: Fujimori, Danica G.
name: Kortemme, Tanja
name: Rakesh, Ramachandran
name: McGregor, Michael J.
name: Obernier, Kirsten
name: Liboy-Lugo, Jose
name: Lin, Yizhu
name: Jura, Natalia
name: Taunton, Jack
name: Huttenhain, Ruth
name: Moreno, Elena
name: Chorba, john S.
name: Shen, Wenqi
name: Gross, John D.
name: Emerman, Michael
name: Hubert, Mathieu
name: Agard, David A.
name: Cakir, Merve
name: Liu, YongFeng
name: Dai, Shizhong
name: Braberg, Hannes
name: Calviello, Lorenzo
name: Fabius, Jacqueline M.
name: Kaake, Robyn M.
name: Polacco, Benjamin J.
name: Mac Kain, Alice
name: Shokat, Kevan M.
name: Rezelj, Veronica V.
name: Cavero, Devin A.
name: Wankowicz, Stephanie A.
name: Soucheray, Margaret
name: Klippsten, Saker
name: Young, Janet M.
name: Ashworth, Alan
name: Rosenberg, Oren S.
name: Frankel, Alan D.
name: Lyu, Jiankun
name: Jang, Gwendolyn M.
name: O'Meara, Matthew J.
name: Salzberg, Daniel J.
name: Miorin, Lisa
name: Eckhardt, Manon
name: Schwartz, Olivier
name: Rathore, Ujjwal
name: Savar, Nastaran Sadat
name: Barrio-Hernandez, Inigo
name: Roth, Bryan L.
name: Noack, Julia
name: Verba, Kliment A.
name: Broadhurst, David J.
name: Swaney, Danielle L.
name: Bohn, Markus
name: Richards, Alicia L.
name: Floor, Stephen N.
name: Gordon, David E.
name: Roth, Theodore
name: Kirby, Ilsa T.
name: Tummino, Tia A.
name: Ganesan, Sai J.
name: Batra, Jyoti
name: Melnyk, James E.
name: Kim, Minkyu
name: Modak, Maya
name: Fraser, James S.
name: Shi, Ying
name: Koh, Cassandra
name: Zhou, Yuan
name: Wenzell, Nicole A.
name: Jacobsen, Matt
name: White, Kris M.
name: Mukherjee, Shaeri
name: Ruggero, Davide
name: Cai, yiming
name: Perica, Tina
name: Naig, Zun Zar Chi
name: Hernandez-Armenta, Claudia
name: Rosenthal, Sara B.
name: Wang, Hao-Yuan
name: Zhang, Ziyang
name: Bennett, Melanie J.
name: O'Neal, Michael C.
name: Safari, Maliheh
name: Liu, Xi
name: Shoichet, Brian K.
name: Haas, Paige
name: Gou, Jeffrey Z.
name: Fletcher, Sabrina J.
name: Subramanian, Adavait
name: Vallet, Thomas
name: Trenker, Raphael
name: Pilla, Kala B.
name: Shengjuler, Djoshkun
name: von Zastrow, Mark
name: Huang, Xi-Ping
name: Sharp, Phillip P.
name: Meyer, Bjoern
name: Malik, Harmit S.
name: Tutuncuoglu, Beril
name: Bouhaddou, Mehdi
name: Garcia-Sastre, Adolfo
name: d'Enfert, Christophe
name: Li, Qiongyu
name: Roesch, Ferdinand
name: Foussard, Helene
name: Ott, Melanie
name: Memon, Danish
name: Ideker, Trey
name: Tran, Quang Dinh
name: Venkataramanan, Srivats
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2020

description: 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.