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Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms.
Gordon, David E; Hiatt, Joseph; Bouhaddou, Mehdi; Rezelj, Veronica V; Ulferts, Svenja; Braberg, Hannes; Jureka, Alexander S; Obernier, Kirsten; Guo, Jeffrey Z; Batra, Jyoti; Kaake, Robyn M; Weckstein, Andrew R; Owens, Tristan W; Gupta, Meghna; Pourmal, Sergei; Titus, Erron W; Cakir, Merve; Soucheray, Margaret; McGregor, Michael; Cakir, Zeynep; Jang, Gwendolyn; O'Meara, Matthew J; Tummino, Tia A; Zhang, Ziyang; Foussard, Helene; Rojc, Ajda; Zhou, Yuan; Kuchenov, Dmitry; Hüttenhain, Ruth; Xu, Jiewei; Eckhardt, Manon; Swaney, Danielle L; Fabius, Jacqueline M; Ummadi, Manisha; Tutuncuoglu, Beril; Rathore, Ujjwal; Modak, Maya; Haas, Paige; Haas, Kelsey M; Naing, Zun Zar Chi; Pulido, Ernst H; Shi, Ying; Barrio-Hernandez, Inigo; Memon, Danish; Petsalaki, Eirini; Dunham, Alistair; Marrero, Miguel Correa; Burke, David; Koh, Cassandra; Vallet, Thomas.
  • Gordon DE; Quantitative Biosciences Institute (QBI) COVID-19 Research Group (QCRG), San Francisco, CA 94158, USA.
  • Hiatt J; QBI, University of California, San Francisco, CA 94158, USA.
  • Bouhaddou M; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
  • Rezelj VV; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Ulferts S; Quantitative Biosciences Institute (QBI) COVID-19 Research Group (QCRG), San Francisco, CA 94158, USA.
  • Braberg H; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Jureka AS; Medical Scientist Training Program, University of California, San Francisco, CA 94143, USA.
  • Obernier K; Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA.
  • Guo JZ; Biomedical Sciences Graduate Program, University of California, San Francisco, CA 94143, USA.
  • Batra J; Quantitative Biosciences Institute (QBI) COVID-19 Research Group (QCRG), San Francisco, CA 94158, USA.
  • Kaake RM; QBI, University of California, San Francisco, CA 94158, USA.
  • Weckstein AR; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
  • Owens TW; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Gupta M; Viral Populations and Pathogenesis Unit, CNRS UMR 3569, Institut Pasteur, 75724, Paris, cedex 15, France.
  • Pourmal S; Institute for Clinical and Experimental Pharmacology and Toxicology I, University of Freiburg, 79104 Freiburg, Germany.
  • Titus EW; Quantitative Biosciences Institute (QBI) COVID-19 Research Group (QCRG), San Francisco, CA 94158, USA.
  • Cakir M; QBI, University of California, San Francisco, CA 94158, USA.
  • Soucheray M; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
  • McGregor M; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Cakir Z; Center for Microbial Pathogenesis, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
  • Jang G; Quantitative Biosciences Institute (QBI) COVID-19 Research Group (QCRG), San Francisco, CA 94158, USA.
  • O'Meara MJ; QBI, University of California, San Francisco, CA 94158, USA.
  • Tummino TA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
  • Zhang Z; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Foussard H; Quantitative Biosciences Institute (QBI) COVID-19 Research Group (QCRG), San Francisco, CA 94158, USA.
  • Rojc A; QBI, University of California, San Francisco, CA 94158, USA.
  • Zhou Y; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
  • Kuchenov D; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Hüttenhain R; Quantitative Biosciences Institute (QBI) COVID-19 Research Group (QCRG), San Francisco, CA 94158, USA.
  • Xu J; QBI, University of California, San Francisco, CA 94158, USA.
  • Eckhardt M; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
  • Swaney DL; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Fabius JM; Quantitative Biosciences Institute (QBI) COVID-19 Research Group (QCRG), San Francisco, CA 94158, USA.
  • Ummadi M; QBI, University of California, San Francisco, CA 94158, USA.
  • Tutuncuoglu B; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
  • Rathore U; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Modak M; Aetion, Inc., New York, NY 10001, USA.
  • Haas P; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Haas KM; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Naing ZZC; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Pulido EH; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Shi Y; Quantitative Biosciences Institute (QBI) COVID-19 Research Group (QCRG), San Francisco, CA 94158, USA.
  • Barrio-Hernandez I; QBI, University of California, San Francisco, CA 94158, USA.
  • Memon D; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
  • Petsalaki E; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Dunham A; Quantitative Biosciences Institute (QBI) COVID-19 Research Group (QCRG), San Francisco, CA 94158, USA.
  • Marrero MC; QBI, University of California, San Francisco, CA 94158, USA.
  • Burke D; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
  • Koh C; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Vallet T; Quantitative Biosciences Institute (QBI) COVID-19 Research Group (QCRG), San Francisco, CA 94158, USA.
Science ; 370(6521)2020 12 04.
Article in English | MEDLINE | ID: covidwho-873450
ABSTRACT
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 ORF9b, an interaction we structurally characterized using cryo-electron microscopy. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified molecular mechanisms and potential drug treatments that merit further molecular and clinical study.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Severe Acute Respiratory Syndrome / Mitochondrial Membrane Transport Proteins / Severe acute respiratory syndrome-related coronavirus / Protein Interaction Maps / Host Microbial Interactions / Coronavirus Nucleocapsid Proteins / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Limits: Humans Language: English Year: 2020 Document Type: Article Affiliation country: Science.abe9403

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Severe Acute Respiratory Syndrome / Mitochondrial Membrane Transport Proteins / Severe acute respiratory syndrome-related coronavirus / Protein Interaction Maps / Host Microbial Interactions / Coronavirus Nucleocapsid Proteins / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Limits: Humans Language: English Year: 2020 Document Type: Article Affiliation country: Science.abe9403