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
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TLDR
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.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.read more
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Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review.
TL;DR: The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918 and both the need and capability to produce high-quality evidence even in the middle of a pandemic.
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Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant.
Maria Pachetti,Maria Pachetti,Bruna Marini,Francesca Benedetti,Fabiola Giudici,Elisabetta Mauro,Paola Storici,Claudio Masciovecchio,Silvia Angeletti,Massimo Ciccozzi,Robert C. Gallo,Robert C. Gallo,Davide Zella,Davide Zella,Rudy Ippodrino +14 more
TL;DR: The findings suggest that the virus is evolving and European, North American and Asian strains might coexist, each of them characterized by a different mutation pattern.
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The Global Phosphorylation Landscape of SARS-CoV-2 Infection.
Mehdi Bouhaddou,Danish Memon,Bjoern Meyer,Kris M. White,Veronica V. Rezelj,Miguel Correa Marrero,Benjamin J. Polacco,James E. Melnyk,Svenja Ulferts,Robyn M. Kaake,Jyoti Batra,Alicia L. Richards,Erica Stevenson,David E. Gordon,Ajda Rojc,Kirsten Obernier,Jacqueline M. Fabius,Margaret Soucheray,Lisa Miorin,Elena Moreno,Cassandra Koh,Quang Dinh Tran,Alexandra Hardy,Rémy Robinot,Thomas Vallet,Benjamin E. Nilsson-Payant,Claudia Hernandez-Armenta,Alistair Dunham,Sebastian Weigang,Julian Knerr,Maya Modak,Diego Quintero,Yuan Zhou,Aurelien Dugourd,Alberto Valdeolivas,Trupti Patil,Qiongyu Li,Ruth Hüttenhain,Merve Cakir,Monita Muralidharan,Minkyu Kim,Gwendolyn M. Jang,Beril Tutuncuoglu,Joseph Hiatt,Jeffrey Z. Guo,Jiewei Xu,Sophia Bouhaddou,Christopher J.P. Mathy,Anna Gaulton,Emma J. Manners,Eloy Felix,Ying Shi,Marisa Goff,Jean K. Lim,Timothy McBride,Michael C. O’Neal,Yiming Cai,Jason C.J. Chang,David J. Broadhurst,Saker Klippsten,Emmie de Wit,Andrew R. Leach,Tanja Kortemme,Brian K. Shoichet,Melanie Ott,Julio Saez-Rodriguez,Benjamin R. tenOever,R. Dyche Mullins,Elizabeth R. Fischer,Georg Kochs,Robert Grosse,Adolfo García-Sastre,Marco Vignuzzi,Jeffery R. Johnson,Kevan M. Shokat,Danielle L. Swaney,Pedro Beltrao,Nevan J. Krogan +77 more
TL;DR: A quantitative mass spectrometry-based phosphoproteomics survey of SARS-CoV-2 infection in Vero E6 cells reveals dramatic rewiring of phosphorylation on host and viral proteins, revealing potential COVID-19 therapies.
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Emergence of genomic diversity and recurrent mutations in SARS-CoV-2.
Lucy van Dorp,Mislav Acman,Damien Richard,Liam P. Shaw,Charlotte Ford,Louise Ormond,Christopher J. Owen,Juanita Pang,Cedric C.S. Tan,Florencia A.T. Boshier,Arturo Torres Ortiz,Francois Balloux +11 more
TL;DR: The results are in line with previous estimates and point to all sequences sharing a common ancestor towards the end of 2019, supporting this as the period when SARS-CoV-2 jumped into its human host.
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Toward Nanotechnology-Enabled Approaches against the COVID-19 Pandemic.
Carsten Weiss,Marie Carrière,Laura Fusco,Laura Fusco,Ilaria Capua,Jose Angel Regla-Nava,Matteo Pasquali,James A. Scott,Flavia Vitale,Flavia Vitale,Mehmet Ünal,Cecilia Mattevi,Davide Bedognetti,Arben Merkoçi,Arben Merkoçi,Ennio Tasciotti,Ennio Tasciotti,Açelya Yilmazer,Yury Gogotsi,Francesco Stellacci,Lucia Gemma Delogu +20 more
TL;DR: Nanoimmunity by design can help to design materials for immune modulation, either stimulating or suppressing the immune response, which would find applications in the context of vaccine development for SARS-CoV-2 or in counteracting the cytokine storm, respectively.
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