2. Academic Validation
  3. A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing

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

  • bioRxiv. 2020 Mar 22;2020.03.22.002386. doi: 10.1101/2020.03.22.002386.
David E Gordon 1 2 3 4,  Gwendolyn M Jang 1 2 3 4,  Mehdi Bouhaddou 1 2 3 4,  Jiewei Xu 1 2 3 4,  Kirsten Obernier 1 2 3 4,  Matthew J O'Meara 5,  Jeffrey Z Guo 1 2 3 4,  Danielle L Swaney 1 2 3 4,  Tia A Tummino 1 2 6,  Ruth Hüttenhain 1 2 3 4,  Robyn M Kaake 1 2 3 4,  Alicia L Richards 1 2 3 4,  Beril Tutuncuoglu 1 2 3 4,  Helene Foussard 1 2 3 4,  Jyoti Batra 1 2 3 4,  Kelsey Haas 1 2 3 4,  Maya Modak 1 2 3 4,  Minkyu Kim 1 2 3 4,  Paige Haas 1 2 3 4,  Benjamin J Polacco 1 2 3 4,  Hannes Braberg 1 2 3 4,  Jacqueline M Fabius 1 2 3 4,  Manon Eckhardt 1 2 3 4,  Margaret Soucheray 1 2 3 4,  Melanie J Bennett 1 2 3 4,  Merve Cakir 1 2 3 4,  Michael J McGregor 1 2 3 4,  Qiongyu Li 1 2 3 4,  Zun Zar Chi Naing 1 2 3 4,  Yuan Zhou 1 2 3 4,  Shiming Peng 1 2 6,  Ilsa T Kirby 1 4 7,  James E Melnyk 1 4 7,  John S Chorba 1 4 7,  Kevin Lou 1 4 7,  Shizhong A Dai 1 4 7,  Wenqi Shen 1 4 7,  Ying Shi 1 4 7,  Ziyang Zhang 1 4 7,  Inigo Barrio-Hernandez 8,  Danish Memon 8,  Claudia Hernandez-Armenta 8,  Christopher J P Mathy 1 2 9 10,  Tina Perica 1 2 9,  Kala B Pilla 1 2 9,  Sai J Ganesan 1 2 9,  Daniel J Saltzberg 1 2 9,  Rakesh Ramachandran 1 2 9,  Xi Liu 1 2 6,  Sara B Rosenthal 11,  Lorenzo Calviello 12,  Srivats Venkataramanan 12,  Yizhu Lin 12,  Stephanie A Wankowicz 1 9 13,  Markus Bohn 6,  Raphael Trenker 14,  Janet M Young 15,  Devin Cavero 16 3,  Joe Hiatt 16 3,  Theo Roth 16 3,  Ujjwal Rathore 16 3,  Advait Subramanian 1 17,  Julia Noack 1 17,  Mathieu Hubert 18,  Ferdinand Roesch 19,  Thomas Vallet 19,  Björn Meyer 19,  Kris M White 20,  Lisa Miorin 20,  David Agard 1 21,  Michael Emerman 22,  Davide Ruggero 23 24 4,  Adolfo García-Sastre 20,  Natalia Jura 1 14 4,  Mark von Zastrow 1 2 4 25,  Jack Taunton 1 2 4,  Olivier Schwartz 18,  Marco Vignuzzi 19,  Christophe d'Enfert 26,  Shaeri Mukherjee 1 17,  Matt Jacobson 6,  Harmit S Malik 15,  Danica G Fujimori 1 4 6,  Trey Ideker 27,  Charles S Craik 6 24,  Stephen Floor 12 24,  James S Fraser 1 2 9,  John Gross 1 2 6,  Andrej Sali 1 2 6 9,  Tanja Kortemme 1 9 10 2,  Pedro Beltrao 8,  Kevan Shokat 1 4 7,  Brian K Shoichet 1 2 6,  Nevan J Krogan 1 2 3 4
Affiliations

Affiliations

  • 1 QBI COVID-19 Research Group (QCRG), San Francisco, CA, 94158, USA.
  • 2 University of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, 94158, USA.
  • 3 J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • 4 University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94158, USA.
  • 5 Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA.
  • 6 Department of Pharmaceutical Chemistry, University of California, San Francisco.
  • 7 Howard Hughes Medical Institute.
  • 8 European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • 9 Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco.
  • 10 The UC Berkeley-UCSF Graduate Program in Bioengineering, University of California San Francisco, San Francisco, CA, USA.
  • 11 Center for Computational Biology and Bioinformatics, Department of Medicine, University of California San Diego.
  • 12 Department of Cell and Tissue Biology, University of California, San Francisco.
  • 13 Biophysics Graduate Program, University of California, San Francisco.
  • 14 Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, 94158, USA.
  • 15 Division of Basic Sciences, Fred Hutchinson Cancer Research Center.
  • 16 Medical Scientist Training Program, University of California, San Francisco, CA 94143, USA.
  • 17 George William Hooper Foundation, Department of Microbiology and Immunology, UC San Francisco.
  • 18 Virus and Immunity Unit, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France.
  • 19 Viral Populations and Pathogenesis Unit, CNRS UMR 3569, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris cedex 15, France.
  • 20 Department for Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY.
  • 21 Biochemistry & Biophysics and Quantitative Biosciences Institute UCSF 600 16th St San Francisco, CA 94143.
  • 22 Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98103.
  • 23 Department of Urology, University of California, San Francisco, San Francisco, CA, USA.
  • 24 Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, 94158, USA.
  • 25 University of California San Francisco, Department of Psychiatry, San Francisco, CA, 94158, USA.
  • 26 Direction Scientifique, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris cedex 15, France.
  • 27 Division of Genetics, Department of Medicine, University of California San Diego.
PMID: 32511329 DOI: 10.1101/2020.03.22.002386
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.

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