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,Jeffrey Z. Guo,Danielle L. Swaney,Tia A. Tummino,Tia A. Tummino,Ruth Hüttenhain,Robyn M. Kaake,Alicia L. Richards,Beril Tutuncuoglu,Helene Foussard,Jyoti Batra,Kelsey M. 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 McGregor,Qiongyu Li,Zun Zar Chi Naing,Yuan Zhou,Shiming Peng,Shiming Peng,Ilsa T Kirby,Ilsa T Kirby,James E. Melnyk,James E. Melnyk,John S. Chorba,John S. Chorba,Kevin Lou,Kevin Lou,Shizhong Dai,Shizhong Dai,Wenqi Shen,Wenqi Shen,Ying Shi,Ying Shi,Ziyang Zhang,Ziyang Zhang,Inigo Barrio-Hernandez,Danish Memon,Claudia Hernandez-Armenta,Christopher J.P. Mathy,Tina Perica,Tina Perica,Kala Bharath Pilla,Kala Bharath Pilla,Sai J. Ganesan,Sai J. Ganesan,Daniel J. Saltzberg,Daniel J. Saltzberg,Rakesh Ramachandran,Rakesh Ramachandran,Xi Liu,Xi Liu,Sara Brin Rosenthal,Lorenzo Calviello,Srivats Venkataramanan,Jose Liboy-Lugo,Yizhu Lin,Stephanie A. Wankowicz,Markus Bohn,Phillip P. Sharp,Raphael Trenker,Janet M. Young,Devin A. Cavero,Joseph Hiatt,Joseph Hiatt,Theodore L. Roth,Theodore L. Roth,Ujjwal Rathore,Advait Subramanian,Julia Noack,Mathieu Hubert,Ferdinand Roesch,Thomas Vallet,Bjoern Meyer,Kris M. White,Lisa Miorin,Oren S. Rosenberg,Kliment A. Verba,Kliment A. Verba,David A. Agard,Melanie Ott,Melanie Ott,Michael Emerman,Davide Ruggero,Davide Ruggero,Adolfo García-Sastre,Natalia Jura,Mark von Zastrow,Jack Taunton,Alan Ashworth,Olivier Schwartz,Marco Vignuzzi,Shaeri Mukherjee,Matthew P. Jacobson,Harmit S. Malik,Danica Galonić Fujimori,Danica Galonić Fujimori,Trey Ideker,Charles S. Craik,Stephen N. Floor,James S. Fraser,James S. Fraser,John D. Gross,John D. Gross,Andrej Sali,Tanja Kortemme,Pedro Beltrao,Kevan M. Shokat,Kevan M. Shokat,Brian K. Shoichet,Brian K. Shoichet,Nevan J. Krogan +123 more
TL;DR: 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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Abstract: Author(s): Gordon, David E; Jang, Gwendolyn M; Bouhaddou, Mehdi; Xu, Jiewei; Obernier, Kirsten; O'Meara, Matthew J; Guo, Jeffrey Z; Swaney, Danielle L; Tummino, Tia A; Huttenhain, Ruth; Kaake, Robyn M; Richards, Alicia L; Tutuncuoglu, Beril; Foussard, Helene; Batra, Jyoti; Haas, Kelsey; Modak, Maya; Kim, Minkyu; Haas, Paige; Polacco, Benjamin J; Braberg, Hannes; Fabius, Jacqueline M; Eckhardt, Manon; Soucheray, Margaret; Bennett, Melanie J; Cakir, Merve; McGregor, Michael J; Li, Qiongyu; Naing, Zun Zar Chi; Zhou, Yuan; Peng, Shiming; Kirby, Ilsa T; Melnyk, James E; Chorba, John S; Lou, Kevin; Dai, Shizhong A; Shen, Wenqi; Shi, Ying; Zhang, Ziyang; Barrio-Hernandez, Inigo; Memon, Danish; Hernandez-Armenta, Claudia; Mathy, Christopher JP; Perica, Tina; Pilla, Kala B; Ganesan, Sai J; Saltzberg, Daniel J; Ramachandran, Rakesh; Liu, Xi; Rosenthal, Sara B; Calviello, Lorenzo; Venkataramanan, Srivats; Lin, Yizhu; Wankowicz, Stephanie A; Bohn, Markus; Trenker, Raphael; Young, Janet M; Cavero, Devin; Hiatt, Joe; Roth, Theo; Rathore, Ujjwal; Subramanian, Advait; Noack, Julia; Hubert, Mathieu; Roesch, Ferdinand; Vallet, Thomas; Meyer, Bjorn; White, Kris M; Miorin, Lisa; Agard, David; Emerman, Michael; Ruggero, Davide; Garcia-Sastre, Adolfo; Jura, Natalia; von Zastrow, Mark; Taunton, Jack; Schwartz, Olivier; Vignuzzi, Marco; d'Enfert, Christophe; Mukherjee, Shaeri; Jacobson, Matt; Malik, Harmit S; Fujimori, Danica G; Ideker, Trey; Craik, Charles S | 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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