A SARS-CoV-2 protein interaction map reveals targets for drug repurposing

Autor: Pedro Beltrao, Phillip P. Sharp, Nevan J. Krogan, Sabrina J. Fletcher, Saker Klippsten, Trey Ideker, Melanie Ott, Bryan L. Roth, Xi Liu, Devin A. Cavero, Djoshkun Shengjuler, Christopher J.P. Mathy, Jason C.J. Chang, Theodore L. Roth, Hannes Braberg, Claudia Hernandez-Armenta, Lisa Miorin, Jyoti Batra, Shizhong Dai, Maliheh Safari, Brian K. Shoichet, Danish Memon, Tia A. Tummino, Marco Vignuzzi, Mark von Zastrow, Manon Eckhardt, Alan D. Frankel, Qiongyu Li, Tanja Kortemme, Nicole A. Wenzell, Zun Zar Chi Naing, Ferdinand Roesch, Nastaran Sadat Savar, Mathieu Hubert, Xi Ping Huang, Elena Moreno, Danica Galonić Fujimori, Jeffrey Z. Guo, Natalia Jura, Kirsten Obernier, Kliment A. Verba, Harmit S. Malik, Hao-Yuan Wang, Michael McGregor, Melanie J. Bennett, Julia Noack, Gwendolyn M. Jang, Paige Haas, Alice Mac Kain, Daniel J. Saltzberg, Mehdi Bouhaddou, Ziyang Zhang, Yongfeng Liu, Inigo Barrio-Hernandez, Yiming Cai, Kris M. White, Kelsey M. Haas, Maya Modak, Stephanie A. Wankowicz, Raphael Trenker, Kevan M. Shokat, Fatima S. Ugur, Shiming Peng, Sai J. Ganesan, Shaeri Mukherjee, Yuan Zhou, Minkyu Kim, John D. Gross, Jack Taunton, Alicia L. Richards, John S. Chorba, Margaret Soucheray, Danielle L. Swaney, Benjamin J. Polacco, Alan Ashworth, Wenqi Shen, Adolfo García-Sastre, Merve Cakir, Ujjwal Rathore, Kala Bharath Pilla, Michael C. O’Neal, Ying Shi, Kevin Lou, Cassandra Koh, Stephen N. Floor, Davide Ruggero, Ilsa T Kirby, Srivats Venkataramanan, Ruth Hüttenhain, Olivier Schwartz, Beril Tutuncuoglu, Christophe d'Enfert, Jose Liboy-Lugo, David A. Agard, Charles S. Craik, Veronica V. Rezelj, Tina Perica, Matthew P. Jacobson, Lorenzo Calviello, Eric Verdin, Yizhu Lin, Jiankun Lyu, Jiewei Xu, Joseph Hiatt, Andrej Sali, Oren S. Rosenberg, Markus Bohn, David E. Gordon, James S. Fraser, Sara Brin Rosenthal, Duygu Kuzuoğlu-Öztürk, Robyn M. Kaake, Jacqueline M. Fabius, Matthew J. O’Meara, Quang Dinh Tran, Advait Subramanian, Thomas Vallet, Bjoern Meyer, James E. Melnyk, Robert M. Stroud, Helene Foussard, Rakesh Ramachandran, David J. Broadhurst, Janet M. Young, Michael Emerman
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
viruses
Drug Evaluation
Preclinical
Plasma protein binding
Proteomics
medicine.disease_cause
Mass Spectrometry
0302 clinical medicine
Chlorocebus aethiops
Protein Interaction Mapping
Molecular Targeted Therapy
Protein Interaction Maps
Cloning
Molecular
Letter to the Editor
Coronavirus
Multidisciplinary
3. Good health
Drug repositioning
030220 oncology & carcinogenesis
Host-Pathogen Interactions
Coronavirus Infections
Protein Binding
Pneumonia
Viral
Biology
Antiviral Agents
Virus
Betacoronavirus
Viral Proteins
03 medical and health sciences
Immune system
Protein Domains
medicine
Animals
Humans
Receptors
sigma
Pandemics
Vero Cells
SKP Cullin F-Box Protein Ligases
Innate immune system
SARS-CoV-2
fungi
HEK 293 cells
Drug Repositioning
COVID-19
Virology
Immunity
Innate
COVID-19 Drug Treatment
HEK293 Cells
030104 developmental biology
Protein Biosynthesis
Zdroj: Nature
Schizophrenia Research
ISSN: 1476-4687
0028-0836
DOI: 10.1038/s41586-020-2286-9
Popis: 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. A human–SARS-CoV-2 protein interaction map highlights cellular processes that are hijacked by the virus and that can be targeted by existing drugs, including inhibitors of mRNA translation and predicted regulators of the sigma receptors.
Databáze: OpenAIRE
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