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A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing

Title: A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing
Authors: Gordon, David E; Jang, Gwendolyn M; Bouhaddou, Mehdi; Xu, Jiewei; Obernier, Kirsten; O'Meara, Matthew J; Guo, Jeffrey Z; Swaney, Danielle L; Tummino, Tia A; 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; Naing, Zun Zar Chi; Zhou, Yuan; Peng, Shiming; Kirby, Ilsa T; Melnyk, James E; Chorba, John S; Lou, Kevin; Dai, Shizhong A; Shen, Wenqi; Shi, Ying; Zhang, Ziyang; Barrio-Hernandez, Inigo; Memon, Danish; Hernandez-Armenta, Claudia; Mathy, Christopher JP; Perica, Tina; Pilla, Kala B; Ganesan, Sai J; Saltzberg, Daniel J; Ramachandran, Rakesh; Liu, Xi; Rosenthal, Sara B; Calviello, Lorenzo; Venkataramanan, Srivats; Liboy-Lugo, Jose; Lin, Yizhu; Wankowicz, Stephanie A; Bohn, Markus; Sharp, Phillip P; Trenker, Raphael; Young, Janet M; Cavero, Devin A; Hiatt, Joseph; Roth, Theodore L; Rathore, Ujjwal; Subramanian, Advait; Noack, Julia; Hubert, Mathieu; Roesch, Ferdinand; Vallet, Thomas; Meyer, Björn; White, Kris M; Miorin, Lisa; Rosenberg, Oren S; Verba, Kliment A; Agard, David; Ott, Melanie; Emerman, Michael; Ruggero, Davide; García-Sastre, Adolfo; Jura, Natalia; von Zastrow, Mark; Taunton, Jack; Ashworth, Alan; Schwartz, Olivier; Vignuzzi, Marco; d'Enfert, Christophe; Mukherjee, Shaeri; Jacobson, Matt; Malik, Harmit S; Fujimori, Danica G; Ideker, Trey; Craik, Charles S; Floor, Stephen; Fraser, James S; Gross, John; Sali, Andrej; Kortemme, Tanja; Beltrao, Pedro; Shokat, Kevan; Shoichet, Brian K; Krogan, Nevan J
Source: bioRxiv : the preprint server for biology, vol 1, iss 05-20
Publisher Information: eScholarship, University of California
Publication Year: 2020
Collection: University of California: eScholarship
Subject Terms: 3207 Medical Microbiology (for-2020); 3102 Bioinformatics and Computational Biology (for-2020); 32 Biomedical and Clinical Sciences (for-2020); 31 Biological Sciences (for-2020); Emerging Infectious Diseases (rcdc); Biodefense (rcdc); Lung (rcdc); Coronaviruses (rcdc); Coronaviruses Therapeutics and Interventions (rcdc); Infectious Diseases (rcdc); 2.2 Factors relating to the physical environment (hrcs-rac); 5.1 Pharmaceuticals (hrcs-rac); Infection (hrcs-hc); 3 Good Health and Well Being (sdg)
Subject Geographic: 2020.03.22.002386
Description: An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 290,000 people since the end of 2019, killed over 12,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Unfortunately, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To illuminate this, we cloned, tagged and expressed 26 of the 29 viral proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), which identified 332 high confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 67 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays. The identification of host dependency factors mediating virus infection may provide key insights into effective molecular targets for developing broadly acting antiviral therapeutics against SARS-CoV-2 and other deadly coronavirus strains.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: unknown
Relation: qt9v71w6zc; https://escholarship.org/uc/item/9v71w6zc; https://escholarship.org/content/qt9v71w6zc/qt9v71w6zc.pdf
DOI: 10.1101/2020.03.22.002386
Availability: https://escholarship.org/uc/item/9v71w6zc; https://escholarship.org/content/qt9v71w6zc/qt9v71w6zc.pdf; https://doi.org/10.1101/2020.03.22.002386
Rights: CC-BY
Accession Number: edsbas.6597CD1E
Database: BASE