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A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.
Gordon, David E; Jang, Gwendolyn M; Bouhaddou, Mehdi; Xu, Jiewei; Obernier, Kirsten; White, Kris M; O'Meara, Matthew J; Rezelj, Veronica V; Guo, Jeffrey Z; Swaney, Danielle L; Tummino, Tia A; Hüttenhain, 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; Meyer, Bjoern; Roesch, Ferdinand; Vallet, Thomas; Mac Kain, Alice; Miorin, Lisa; Moreno, Elena; Naing, Zun Zar Chi; Zhou, Yuan; Peng, Shiming; Shi, Ying; Zhang, Ziyang; Shen, Wenqi; Kirby, Ilsa T; Melnyk, James E; Chorba, John S; Lou, Kevin; Dai, Shizhong A; Barrio-Hernandez, Inigo; Memon, Danish; Hernandez-Armenta, Claudia.
  • Gordon DE; QBI COVID-19 Research Group (QCRG), San Francisco, CA, USA.
  • Jang GM; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
  • Bouhaddou M; J. David Gladstone Institutes, San Francisco, CA, USA.
  • Xu J; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
  • Obernier K; QBI COVID-19 Research Group (QCRG), San Francisco, CA, USA.
  • White KM; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
  • O'Meara MJ; J. David Gladstone Institutes, San Francisco, CA, USA.
  • Rezelj VV; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
  • Guo JZ; QBI COVID-19 Research Group (QCRG), San Francisco, CA, USA.
  • Swaney DL; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
  • Tummino TA; J. David Gladstone Institutes, San Francisco, CA, USA.
  • Hüttenhain R; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
  • Kaake RM; QBI COVID-19 Research Group (QCRG), San Francisco, CA, USA.
  • Richards AL; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
  • Tutuncuoglu B; J. David Gladstone Institutes, San Francisco, CA, USA.
  • Foussard H; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
  • Batra J; QBI COVID-19 Research Group (QCRG), San Francisco, CA, USA.
  • Haas K; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
  • Modak M; J. David Gladstone Institutes, San Francisco, CA, USA.
  • Kim M; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
  • Haas P; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Polacco BJ; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Braberg H; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Fabius JM; Viral Populations and Pathogenesis Unit, CNRS UMR 3569, Institut Pasteur, Paris, France.
  • Eckhardt M; QBI COVID-19 Research Group (QCRG), San Francisco, CA, USA.
  • Soucheray M; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
  • Bennett MJ; J. David Gladstone Institutes, San Francisco, CA, USA.
  • Cakir M; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
  • McGregor MJ; QBI COVID-19 Research Group (QCRG), San Francisco, CA, USA.
  • Li Q; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
  • Meyer B; J. David Gladstone Institutes, San Francisco, CA, USA.
  • Roesch F; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
  • Vallet T; QBI COVID-19 Research Group (QCRG), San Francisco, CA, USA.
  • Mac Kain A; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
  • Miorin L; Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.
  • Moreno E; QBI COVID-19 Research Group (QCRG), San Francisco, CA, USA.
  • Naing ZZC; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
  • Zhou Y; J. David Gladstone Institutes, San Francisco, CA, USA.
  • Peng S; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
  • Shi Y; QBI COVID-19 Research Group (QCRG), San Francisco, CA, USA.
  • Zhang Z; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
  • Shen W; J. David Gladstone Institutes, San Francisco, CA, USA.
  • Kirby IT; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
  • Melnyk JE; QBI COVID-19 Research Group (QCRG), San Francisco, CA, USA.
  • Chorba JS; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
  • Lou K; J. David Gladstone Institutes, San Francisco, CA, USA.
  • Dai SA; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
  • Barrio-Hernandez I; QBI COVID-19 Research Group (QCRG), San Francisco, CA, USA.
  • Memon D; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
  • Hernandez-Armenta C; J. David Gladstone Institutes, San Francisco, CA, USA.
Nature ; 583(7816): 459-468, 2020 07.
Article in English | MEDLINE | ID: covidwho-152254
ABSTRACT
A newly described coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 2019 (COVID-19), has infected over 2.3 million people, led to the death of more than 160,000 individuals and caused worldwide social and economic disruption1,2. There are no antiviral drugs with proven clinical efficacy for the treatment of COVID-19, nor are there any vaccines that prevent infection with SARS-CoV-2, and efforts to develop drugs and vaccines are hampered by the limited knowledge of the molecular details of how SARS-CoV-2 infects cells. Here we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins that physically associated with each of the SARS-CoV-2 proteins using affinity-purification mass spectrometry, identifying 332 high-confidence protein-protein interactions between SARS-CoV-2 and human proteins. Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (of which, 29 drugs are approved by the US Food and Drug Administration, 12 are in clinical trials and 28 are preclinical compounds). We screened a subset of these in multiple viral assays and found two sets of pharmacological agents that displayed antiviral activity inhibitors of mRNA translation and predicted regulators of the sigma-1 and sigma-2 receptors. Further studies of these host-factor-targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Viral Proteins / Coronavirus Infections / Drug Repositioning / Molecular Targeted Therapy / Protein Interaction Maps / Betacoronavirus Type of study: Prognostic study Topics: Traditional medicine / Vaccines Limits: Animals / Humans Language: English Journal: Nature Year: 2020 Document Type: Article Affiliation country: S41586-020-2286-9

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Viral Proteins / Coronavirus Infections / Drug Repositioning / Molecular Targeted Therapy / Protein Interaction Maps / Betacoronavirus Type of study: Prognostic study Topics: Traditional medicine / Vaccines Limits: Animals / Humans Language: English Journal: Nature Year: 2020 Document Type: Article Affiliation country: S41586-020-2286-9