TY - JOUR T1 - A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing JF - bioRxiv DO - 10.1101/2020.03.22.002386 SP - 2020.03.22.002386 AU - David E. Gordon AU - Gwendolyn M. Jang AU - Mehdi Bouhaddou AU - Jiewei Xu AU - Kirsten Obernier AU - Matthew J. O’Meara AU - Jeffrey Z. Guo AU - Danielle L. Swaney AU - Tia A. Tummino AU - Ruth Hüttenhain AU - Robyn M. Kaake AU - Alicia L. Richards AU - Beril Tutuncuoglu AU - Helene Foussard AU - Jyoti Batra AU - Kelsey Haas AU - Maya Modak AU - Minkyu Kim AU - Paige Haas AU - Benjamin J. Polacco AU - Hannes Braberg AU - Jacqueline M. Fabius AU - Manon Eckhardt AU - Margaret Soucheray AU - Melanie J. Bennett AU - Merve Cakir AU - Michael J McGregor AU - Qiongyu Li AU - Zun Zar Chi Naing AU - Yuan Zhou AU - Shiming Peng AU - Ilsa T. Kirby AU - James E. Melnyk AU - John S. Chorba AU - Kevin Lou AU - Shizhong A. Dai AU - Wenqi Shen AU - Ying Shi AU - Ziyang Zhang AU - Inigo Barrio-Hernandez AU - Danish Memon AU - Claudia Hernandez-Armenta AU - Christopher J.P. Mathy AU - Tina Perica AU - Kala B. Pilla AU - Sai J. Ganesan AU - Daniel J. Saltzberg AU - Rakesh Ramachandran AU - Xi Liu AU - Sara B. Rosenthal AU - Lorenzo Calviello AU - Srivats Venkataramanan AU - Yizhu Lin AU - Stephanie A. Wankowicz AU - Markus Bohn AU - Raphael Trenker AU - Janet M. Young AU - Devin Cavero AU - Joe Hiatt AU - Theo Roth AU - Ujjwal Rathore AU - Advait Subramanian AU - Julia Noack AU - Mathieu Hubert AU - Ferdinand Roesch AU - Thomas Vallet AU - Björn Meyer AU - Kris M. White AU - Lisa Miorin AU - David Agard AU - Michael Emerman AU - Davide Ruggero AU - Adolfo García-Sastre AU - Natalia Jura AU - Mark von Zastrow AU - Jack Taunton AU - Olivier Schwartz AU - Marco Vignuzzi AU - Christophe d’Enfert AU - Shaeri Mukherjee AU - Matt Jacobson AU - Harmit S. Malik AU - Danica G. Fujimori AU - Trey Ideker AU - Charles S. Craik AU - Stephen Floor AU - James S. Fraser AU - John Gross AU - Andrej Sali AU - Tanja Kortemme AU - Pedro Beltrao AU - Kevan Shokat AU - Brian K. Shoichet AU - Nevan J. Krogan Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/03/22/2020.03.22.002386.abstract N2 - 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.HC-PPIsHigh confidence protein-protein interactionsPPIsprotein-protein interactionAP-MSaffinity purification-mass spectrometryCOVID-19Coronavirus Disease-2019ACE2angiotensin converting enzyme 2Orfopen reading frameNsp3papain-like proteaseNsp5main proteaseNspnonstructural proteinTPMtranscripts per million ER -