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

David E. Gordon(Gladstone Institutes), Gwendolyn Μ. Jang(Gladstone Institutes), Mehdi Bouhaddou(Gladstone Institutes), Jiewei Xu(Gladstone Institutes), Kirsten Obernier(Gladstone Institutes), Matthew J. O’Meara(University of Michigan), Jeffrey Guo(Gladstone Institutes), Danielle L. Swaney(Gladstone Institutes), Tia A. Tummino(University of California, San Francisco), Ruth Hüttenhain(Gladstone Institutes), Robyn M. Kaake(Gladstone Institutes), Alicia Richards(Gladstone Institutes), Beril Tutuncuoglu(Gladstone Institutes), Helene Foussard(Gladstone Institutes), Jyoti Batra(Gladstone Institutes), Kelsey M. Haas(Gladstone Institutes), Maya Modak(Gladstone Institutes), Minkyu Kim(Gladstone Institutes), Paige Haas(Gladstone Institutes), Benjamin J. Polacco(Gladstone Institutes), Hannes Braberg(Gladstone Institutes), Jacqueline M. Fabius(Gladstone Institutes), Manon Eckhardt(Gladstone Institutes), Margaret Soucheray(Gladstone Institutes), Melanie J. Bennett(Gladstone Institutes), Merve Çakır(Gladstone Institutes), Michael McGregor(Gladstone Institutes), Qiongyu Li(Gladstone Institutes), Zun Zar Chi Naing(Gladstone Institutes), Yuan Zhou(Gladstone Institutes), Shiming Peng(University of California, San Francisco), Ilsa T. Kirby(Howard Hughes Medical Institute), James E. Melnyk(Howard Hughes Medical Institute), John S. Chorba(Howard Hughes Medical Institute), Kevin Lou(Howard Hughes Medical Institute), Shizhong Dai(Howard Hughes Medical Institute), Wenqi Shen(Howard Hughes Medical Institute), Ying Shi(Howard Hughes Medical Institute), Ziyang Zhang(Howard Hughes Medical Institute), Inigo Barrio‐Hernandez(European Bioinformatics Institute), Danish Memon(European Bioinformatics Institute), Claudia Hernández-Armenta(European Bioinformatics Institute), Christopher J.P. Mathy(University of California, San Francisco), Tina Perica(University of California, San Francisco), Kala Bharath Pilla(University of California, San Francisco), Sai J. Ganesan(University of California, San Francisco), Daniel J. Saltzberg(University of California, San Francisco), Ramachandran Rakesh(University of California, San Francisco), Xi Liu(University of California, San Francisco), Sara B. Rosenthal(University of California San Diego), Lorenzo Calviello(University of California, San Francisco), Srivats Venkataramanan(University of California, San Francisco), José Liboy-Lugo(University of California, San Francisco), Yizhu Lin(University of California, San Francisco), Stephanie A. Wankowicz(University of California, San Francisco), Markus‐Frederik Bohn(University of California, San Francisco), Phillip P. Sharp(University of California, San Francisco), Raphael Trenker(University of California, San Francisco), Janet M. Young(Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa), Devin A. Cavero(Gladstone Institutes), Joseph Hiatt(Gladstone Institutes), Theodore L. Roth(Gladstone Institutes), Ujjwal Rathore(Gladstone Institutes), Advait Subramanian(San Francisco Foundation), Julia Noack(San Francisco Foundation), Mathieu Hubert(Institut Pasteur), Ferdinand Roesch(Centre National de la Recherche Scientifique), Thomas Vallet(Centre National de la Recherche Scientifique), Bjoern Meyer(Centre National de la Recherche Scientifique), Kris M. White(Icahn School of Medicine at Mount Sinai), Lisa Miorin(Icahn School of Medicine at Mount Sinai), Oren S. Rosenberg(University of California, San Francisco), Kliment A. Verba(University of California, San Francisco), David A. Agard(Quality Biological), Mélanie Ott(Gladstone Institutes), Michael Emerman(Fred Hutch Cancer Center), Davide Ruggero(University of California, San Francisco), Adolfo García‐Sastre(Icahn School of Medicine at Mount Sinai), Natalia Jura(University of California, San Francisco), Mark von Zastrow(University of California, San Francisco), Jack Taunton(University of California, San Francisco), Alan Ashworth(University of California, San Francisco), Olivier Schwartz(Institut Pasteur), Marco Vignuzzi(Centre National de la Recherche Scientifique), Christophe d’Enfert(Institut Pasteur), Shaeri Mukherjee(San Francisco Foundation), Matthew P. Jacobson(University of California, San Francisco), Harmit S. Malik(Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa), Danica Galonić Fujimori(University of California, San Francisco), Trey Ideker(University of California San Diego), Charles S. Craik(University of California, San Francisco), Stephen N. Floor(University of California, San Francisco), James S. Fraser(University of California, San Francisco), John D. Gross(University of California, San Francisco), Andrej Šali(University of California, San Francisco), Tanja Kortemme(University of California, San Francisco), Pedro Beltrão(European Bioinformatics Institute), Kevan M. Shokat(Howard Hughes Medical Institute), Brian K. Shoichet(University of California, San Francisco), Nevan J. Krogan(Gladstone Institutes)
bioRxiv (Cold Spring Harbor Laboratory)
March 22, 2020
10.1101/2020.03.22.002386
Cited by 455Open Access
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Abstract

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 67 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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