New Results
A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing
David E. Gordon, View ORCID ProfileGwendolyn M. Jang, View ORCID ProfileMehdi Bouhaddou, View ORCID ProfileJiewei Xu, View ORCID ProfileKirsten Obernier, View ORCID ProfileMatthew J. O’Meara, Jeffrey Z. Guo, View ORCID ProfileDanielle L. Swaney, View ORCID ProfileTia A. Tummino, View ORCID ProfileRuth Hüttenhain, View ORCID ProfileRobyn M. Kaake, View ORCID ProfileAlicia L. Richards, View ORCID ProfileBeril Tutuncuoglu, Helene Foussard, View ORCID ProfileJyoti Batra, View ORCID ProfileKelsey Haas, View ORCID ProfileMaya Modak, View ORCID ProfileMinkyu Kim, View ORCID ProfilePaige Haas, View ORCID ProfileBenjamin J. Polacco, View ORCID ProfileHannes Braberg, Jacqueline M. Fabius, View ORCID ProfileManon Eckhardt, View ORCID ProfileMargaret Soucheray, Melanie J. Bennett, View ORCID ProfileMerve Cakir, View ORCID ProfileMichael J McGregor, View ORCID ProfileQiongyu Li, View ORCID ProfileZun Zar Chi Naing, View ORCID ProfileYuan Zhou, Shiming Peng, View ORCID ProfileIlsa T. Kirby, View ORCID ProfileJames E. Melnyk, View ORCID ProfileJohn S. Chorba, View ORCID ProfileKevin Lou, View ORCID ProfileShizhong A. Dai, View ORCID ProfileWenqi Shen, View ORCID ProfileYing Shi, View ORCID ProfileZiyang Zhang, View ORCID ProfileInigo Barrio-Hernandez, View ORCID ProfileDanish Memon, View ORCID ProfileClaudia Hernandez-Armenta, View ORCID ProfileChristopher J.P. Mathy, View ORCID ProfileTina Perica, View ORCID ProfileKala B. Pilla, View ORCID ProfileSai J. Ganesan, View ORCID ProfileDaniel J. Saltzberg, View ORCID ProfileRakesh Ramachandran, Xi Liu, View ORCID ProfileSara B. Rosenthal, View ORCID ProfileLorenzo Calviello, View ORCID ProfileSrivats Venkataramanan, View ORCID ProfileYizhu Lin, View ORCID ProfileStephanie A. Wankowicz, View ORCID ProfileMarkus Bohn, View ORCID ProfileRaphael Trenker, View ORCID ProfileJanet M. Young, View ORCID ProfileDevin Cavero, View ORCID ProfileJoe Hiatt, View ORCID ProfileTheo Roth, View ORCID ProfileUjjwal Rathore, View ORCID ProfileAdvait Subramanian, Julia Noack, Mathieu Hubert, Ferdinand Roesch, Thomas Vallet, Björn Meyer, View ORCID ProfileKris M. White, View ORCID ProfileLisa Miorin, View ORCID ProfileDavid Agard, View ORCID ProfileMichael Emerman, View ORCID ProfileDavide Ruggero, View ORCID ProfileAdolfo García-Sastre, View ORCID ProfileNatalia Jura, View ORCID ProfileMark von Zastrow, View ORCID ProfileJack Taunton, View ORCID ProfileOlivier Schwartz, View ORCID ProfileMarco Vignuzzi, View ORCID ProfileChristophe d’Enfert, View ORCID ProfileShaeri Mukherjee, Matt Jacobson, View ORCID ProfileHarmit S. Malik, View ORCID ProfileDanica G. Fujimori, View ORCID ProfileTrey Ideker, View ORCID ProfileCharles S. Craik, View ORCID ProfileStephen Floor, View ORCID ProfileJames S. Fraser, View ORCID ProfileJohn Gross, View ORCID ProfileAndrej Sali, View ORCID ProfileTanja Kortemme, View ORCID ProfilePedro Beltrao, View ORCID ProfileKevan Shokat, View ORCID ProfileBrian K. Shoichet, View ORCID ProfileNevan J. Krogan
doi: https://doi.org/10.1101/2020.03.22.002386
David E. Gordon
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Gwendolyn M. Jang
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Mehdi Bouhaddou
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Jiewei Xu
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Kirsten Obernier
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Matthew J. O’Meara
5Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA
Jeffrey Z. Guo
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Danielle L. Swaney
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Tia A. Tummino
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
6Department of Pharmaceutical Chemistry, University of California, San Francisco
Ruth Hüttenhain
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Robyn M. Kaake
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Alicia L. Richards
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Beril Tutuncuoglu
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Helene Foussard
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Jyoti Batra
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Kelsey Haas
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Maya Modak
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Minkyu Kim
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Paige Haas
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Benjamin J. Polacco
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Hannes Braberg
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Jacqueline M. Fabius
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Manon Eckhardt
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Margaret Soucheray
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Melanie J. Bennett
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Merve Cakir
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Michael J McGregor
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Qiongyu Li
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Zun Zar Chi Naing
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Yuan Zhou
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Shiming Peng
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
6Department of Pharmaceutical Chemistry, University of California, San Francisco
Ilsa T. Kirby
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
7Howard Hughes Medical Institute
James E. Melnyk
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
7Howard Hughes Medical Institute
John S. Chorba
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
7Howard Hughes Medical Institute
Kevin Lou
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
7Howard Hughes Medical Institute
Shizhong A. Dai
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
7Howard Hughes Medical Institute
Wenqi Shen
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
7Howard Hughes Medical Institute
Ying Shi
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
7Howard Hughes Medical Institute
Ziyang Zhang
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
7Howard Hughes Medical Institute
Inigo Barrio-Hernandez
8European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK
Danish Memon
8European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK
Claudia Hernandez-Armenta
8European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK
Christopher J.P. Mathy
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
9Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco
10The UC Berkeley-UCSF Graduate Program in Bioengineering, University of California San Francisco, San Francisco, CA, USA
Tina Perica
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
9Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco
Kala B. Pilla
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
9Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco
Sai J. Ganesan
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
9Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco
Daniel J. Saltzberg
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
9Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco
Rakesh Ramachandran
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
9Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco
Xi Liu
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
6Department of Pharmaceutical Chemistry, University of California, San Francisco
Sara B. Rosenthal
11Center for Computational Biology and Bioinformatics, Department of Medicine, University of California San Diego
Lorenzo Calviello
12Department of Cell and Tissue Biology, University of California, San Francisco
Srivats Venkataramanan
12Department of Cell and Tissue Biology, University of California, San Francisco
Yizhu Lin
12Department of Cell and Tissue Biology, University of California, San Francisco
Stephanie A. Wankowicz
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
9Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco
13Biophysics Graduate Program, University of California, San Francisco
Markus Bohn
6Department of Pharmaceutical Chemistry, University of California, San Francisco
Raphael Trenker
14Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, 94158, USA
Janet M. Young
15Division of Basic Sciences, Fred Hutchinson Cancer Research Center
Devin Cavero
16Medical Scientist Training Program, University of California, San Francisco, CA 94143, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
Joe Hiatt
16Medical Scientist Training Program, University of California, San Francisco, CA 94143, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
Theo Roth
16Medical Scientist Training Program, University of California, San Francisco, CA 94143, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
Ujjwal Rathore
16Medical Scientist Training Program, University of California, San Francisco, CA 94143, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
Advait Subramanian
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
17George William Hooper Foundation, Department of Microbiology and Immunology, UC San Francisco
Julia Noack
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
17George William Hooper Foundation, Department of Microbiology and Immunology, UC San Francisco
Mathieu Hubert
18Virus and Immunity Unit, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France
Ferdinand Roesch
19Viral Populations and Pathogenesis Unit, CNRS UMR 3569, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris cedex 15, France
Thomas Vallet
19Viral Populations and Pathogenesis Unit, CNRS UMR 3569, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris cedex 15, France
Björn Meyer
19Viral Populations and Pathogenesis Unit, CNRS UMR 3569, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris cedex 15, France
Kris M. White
20Department for Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY
Lisa Miorin
20Department for Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY
David Agard
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
21Biochemistry & Biophysics and Quantitative Biosciences Institute UCSF 600 16th St San Francisco, CA 94143
Michael Emerman
22Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98103
Davide Ruggero
23Department of Urology, University of California, San Francisco, San Francisco, CA, USA
24Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Adolfo García-Sastre
20Department for Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY
Natalia Jura
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
14Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Mark von Zastrow
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
25University of California San Francisco, Department of Psychiatry, San Francisco, CA, 94158, USA
Jack Taunton
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
Olivier Schwartz
18Virus and Immunity Unit, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France
Marco Vignuzzi
19Viral Populations and Pathogenesis Unit, CNRS UMR 3569, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris cedex 15, France
Christophe d’Enfert
26Direction Scientifique, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris cedex 15, France
Shaeri Mukherjee
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
17George William Hooper Foundation, Department of Microbiology and Immunology, UC San Francisco
Matt Jacobson
6Department of Pharmaceutical Chemistry, University of California, San Francisco
Harmit S. Malik
15Division of Basic Sciences, Fred Hutchinson Cancer Research Center
Danica G. Fujimori
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
6Department of Pharmaceutical Chemistry, University of California, San Francisco
Trey Ideker
27Division of Genetics, Department of Medicine, University of California San Diego
Charles S. Craik
6Department of Pharmaceutical Chemistry, University of California, San Francisco
24Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, 94158, USA
Stephen Floor
12Department of Cell and Tissue Biology, University of California, San Francisco
24Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, 94158, USA
James S. Fraser
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
9Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco
John Gross
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
6Department of Pharmaceutical Chemistry, University of California, San Francisco
Andrej Sali
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
6Department of Pharmaceutical Chemistry, University of California, San Francisco
9Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco
Tanja Kortemme
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
9Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco
10The UC Berkeley-UCSF Graduate Program in Bioengineering, University of California San Francisco, San Francisco, CA, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
Pedro Beltrao
8European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK
Kevan Shokat
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
7Howard Hughes Medical Institute
Brian K. Shoichet
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
6Department of Pharmaceutical Chemistry, University of California, San Francisco
Nevan J. Krogan
1QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA
2University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA
3J. David Gladstone Institutes, San Francisco, CA 94158, USA
4University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA
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.
Footnotes
Conflicts: The Krogan Laboratory has received research support from Vir Biotechnology and F. Hoffmann-La Roche. Kevan Shokat has consulting agreements for the following companies involving cash and/or stock compensation: Black Diamond Therapeutics, BridGene Biosciences, Denali Therapeutics, Dice Molecules, eFFECTOR Therapeutics, Erasca, Genentech/Roche, Janssen Pharmaceuticals, Kumquat Biosciences, Kura Oncology, Merck, Mitokinin, Petra Pharma, Qulab Inc. Revolution Medicines, Type6 Therapeutics, Venthera, Wellspring Biosciences (Araxes Pharma). Jack Taunton is a cofounder and shareholder of Global Blood Therapeutics, Principia Biopharma, Kezar Life Sciences, and Cedilla Therapeutics. Jack Taunton and Phillip P. Sharp are listed as inventors on a provisional patent application describing PS3061.
Abbreviations
- HC-PPIs
- High confidence protein-protein interactions
- PPIs
- protein-protein interaction
- AP-MS
- affinity purification-mass spectrometry
- COVID-19
- Coronavirus Disease-2019
- ACE2
- angiotensin converting enzyme 2
- Orf
- open reading frame
- Nsp3
- papain-like protease
- Nsp5
- main protease
- Nsp
- nonstructural protein
- TPM
- transcripts per million
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Posted March 22, 2020.
A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing
David E. Gordon, Gwendolyn M. Jang, Mehdi Bouhaddou, Jiewei Xu, Kirsten Obernier, Matthew J. O’Meara, Jeffrey Z. Guo, Danielle L. Swaney, Tia A. Tummino, Ruth Hüttenhain, Robyn M. Kaake, Alicia L. Richards, Beril Tutuncuoglu, Helene Foussard, Jyoti Batra, Kelsey Haas, Maya Modak, Minkyu Kim, Paige Haas, Benjamin J. Polacco, Hannes Braberg, Jacqueline M. Fabius, Manon Eckhardt, Margaret Soucheray, Melanie J. Bennett, Merve Cakir, Michael J McGregor, Qiongyu Li, Zun Zar Chi Naing, Yuan Zhou, Shiming Peng, Ilsa T. Kirby, James E. Melnyk, John S. Chorba, Kevin Lou, Shizhong A. Dai, Wenqi Shen, Ying Shi, Ziyang Zhang, Inigo Barrio-Hernandez, Danish Memon, Claudia Hernandez-Armenta, Christopher J.P. Mathy, Tina Perica, Kala B. Pilla, Sai J. Ganesan, Daniel J. Saltzberg, Rakesh Ramachandran, Xi Liu, Sara B. Rosenthal, Lorenzo Calviello, Srivats Venkataramanan, Yizhu Lin, Stephanie A. Wankowicz, Markus Bohn, Raphael Trenker, Janet M. Young, Devin Cavero, Joe Hiatt, Theo Roth, Ujjwal Rathore, Advait Subramanian, Julia Noack, Mathieu Hubert, Ferdinand Roesch, Thomas Vallet, Björn Meyer, Kris M. White, Lisa Miorin, David Agard, Michael Emerman, Davide Ruggero, Adolfo García-Sastre, Natalia Jura, Mark von Zastrow, Jack Taunton, Olivier Schwartz, Marco Vignuzzi, Christophe d’Enfert, Shaeri Mukherjee, Matt Jacobson, Harmit S. Malik, Danica G. Fujimori, Trey Ideker, Charles S. Craik, Stephen Floor, James S. Fraser, John Gross, Andrej Sali, Tanja Kortemme, Pedro Beltrao, Kevan Shokat, Brian K. Shoichet, Nevan J. Krogan
bioRxiv 2020.03.22.002386; doi: https://doi.org/10.1101/2020.03.22.002386
A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing
David E. Gordon, Gwendolyn M. Jang, Mehdi Bouhaddou, Jiewei Xu, Kirsten Obernier, Matthew J. O’Meara, Jeffrey Z. Guo, Danielle L. Swaney, Tia A. Tummino, Ruth Hüttenhain, Robyn M. Kaake, Alicia L. Richards, Beril Tutuncuoglu, Helene Foussard, Jyoti Batra, Kelsey Haas, Maya Modak, Minkyu Kim, Paige Haas, Benjamin J. Polacco, Hannes Braberg, Jacqueline M. Fabius, Manon Eckhardt, Margaret Soucheray, Melanie J. Bennett, Merve Cakir, Michael J McGregor, Qiongyu Li, Zun Zar Chi Naing, Yuan Zhou, Shiming Peng, Ilsa T. Kirby, James E. Melnyk, John S. Chorba, Kevin Lou, Shizhong A. Dai, Wenqi Shen, Ying Shi, Ziyang Zhang, Inigo Barrio-Hernandez, Danish Memon, Claudia Hernandez-Armenta, Christopher J.P. Mathy, Tina Perica, Kala B. Pilla, Sai J. Ganesan, Daniel J. Saltzberg, Rakesh Ramachandran, Xi Liu, Sara B. Rosenthal, Lorenzo Calviello, Srivats Venkataramanan, Yizhu Lin, Stephanie A. Wankowicz, Markus Bohn, Raphael Trenker, Janet M. Young, Devin Cavero, Joe Hiatt, Theo Roth, Ujjwal Rathore, Advait Subramanian, Julia Noack, Mathieu Hubert, Ferdinand Roesch, Thomas Vallet, Björn Meyer, Kris M. White, Lisa Miorin, David Agard, Michael Emerman, Davide Ruggero, Adolfo García-Sastre, Natalia Jura, Mark von Zastrow, Jack Taunton, Olivier Schwartz, Marco Vignuzzi, Christophe d’Enfert, Shaeri Mukherjee, Matt Jacobson, Harmit S. Malik, Danica G. Fujimori, Trey Ideker, Charles S. Craik, Stephen Floor, James S. Fraser, John Gross, Andrej Sali, Tanja Kortemme, Pedro Beltrao, Kevan Shokat, Brian K. Shoichet, Nevan J. Krogan
bioRxiv 2020.03.22.002386; doi: https://doi.org/10.1101/2020.03.22.002386
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