A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing
| Autor: | David E. Gordon, Gwendolyn M. Jang, Qiongyu Li, Natalia Jura, Sara Brin Rosenthal, Trey Ideker, Paige Haas, Melanie J. Bennett, Ilsa T Kirby, Adolfo García-Sastre, Michael Emerman, Thomas Vallet, Tina Perica, Lorenzo Calviello, Kirsten Obernier, Kliment A. Verba, Tanja Kortemme, Michael McGregor, Alan Ashworth, Ujjwal Rathore, Ziyang Zhang, Kelsey M. Haas, Rakesh Ramachandran, Mark von Zastrow, Jacqueline M. Fabius, Theodore L. Roth, Daniel J. Saltzberg, Matthew P. Jacobson, Kevin Lou, Ferdinand Roesch, Yizhu Lin, John S. Chorba, Beril Tutuncuoglu, Claudia Hernandez-Armenta, Harmit S. Malik, Janet M. Young, Manon Eckhardt, Srivats Venkataramanan, Jose Liboy-Lugo, Phillip P. Sharp, Jeffrey Z. Guo, Maya Modak, Shaeri Mukherjee, Markus Bohn, Brian K. Shoichet, Olivier Schwartz, Jiewei Xu, James S. Fraser, Andrej Sali, Oren S. Rosenberg, Christopher J.P. Mathy, Charles S. Craik, Benjamin J. Polacco, Melanie Ott, Sai J. Ganesan, Pedro Beltrao, Alicia L. Richards, Helene Foussard, Margaret Soucheray, Joseph Hiatt, Robyn M. Kaake, Danielle L. Swaney, Wenqi Shen, Bjoern Meyer, Kala Bharath Pilla, Zun Zar Chi Naing, Marco Vignuzzi, James E. Melnyk, John D. Gross, Shiming Peng, Mehdi Bouhaddou, Nevan J. Krogan, Merve Cakir, Mathieu Hubert, Stephanie A. Wankowicz, Ying Shi, Davide Ruggero, Kevan M. Shokat, Stephen N. Floor, Jack Taunton, Xi Liu, Ruth Hüttenhain, David A. Agard, Lisa Miorin, Danish Memon, Julia Noack, Raphael Trenker, Hannes Braberg, Shizhong Dai, Tia A. Tummino, Kris M. White, Yuan Zhou, Minkyu Kim, Devin A. Cavero, Jyoti Batra, Advait Subramanian, Danica Galonić Fujimori, Inigo Barrio-Hernandez |
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| Rok vydání: | 2020 |
| Předmět: |
Coronavirus disease 2019 (COVID-19)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) media_common.quotation_subject viruses Host factors Article Vaccine Related 03 medical and health sciences 0302 clinical medicine Rare Diseases Biodefense 2.2 Factors relating to the physical environment Aetiology Human proteins Lung 030304 developmental biology media_common 0303 health sciences Prevention Art Pneumonia 3. Good health Good Health and Well Being Infectious Diseases Emerging Infectious Diseases 5.1 Pharmaceuticals 030220 oncology & carcinogenesis Protein Interaction Networks Molecular targets Pneumonia & Influenza Development of treatments and therapeutic interventions Infection Humanities |
| Zdroj: | bioRxiv : the preprint server for biology, vol 1, iss 05-20 bioRxiv article-version (status) pre article-version (number) 1 |
| Popis: | Author(s): 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; Huttenhain, 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; Lin, Yizhu; Wankowicz, Stephanie A; Bohn, Markus; Trenker, Raphael; Young, Janet M; Cavero, Devin; Hiatt, Joe; Roth, Theo; Rathore, Ujjwal; Subramanian, Advait; Noack, Julia; Hubert, Mathieu; Roesch, Ferdinand; Vallet, Thomas; Meyer, Bjorn; White, Kris M; Miorin, Lisa; Agard, David; Emerman, Michael; Ruggero, Davide; Garcia-Sastre, Adolfo; Jura, Natalia; von Zastrow, Mark; Taunton, Jack; Schwartz, Olivier; Vignuzzi, Marco; d'Enfert, Christophe; Mukherjee, Shaeri; Jacobson, Matt; Malik, Harmit S; Fujimori, Danica G; Ideker, Trey; Craik, Charles S | Abstract: 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 66 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. |
| Databáze: | OpenAIRE |
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