A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing PMID: 32511329

ADC Targets in Oncology

2026-04-10

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

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.

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 disruption^1,2. 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.