Your browser doesn't support javascript.
A comprehensive SARS-CoV-2-human protein-protein interactome reveals COVID-19 pathobiology and potential host therapeutic targets.
Zhou, Yadi; Liu, Yuan; Gupta, Shagun; Paramo, Mauricio I; Hou, Yuan; Mao, Chengsheng; Luo, Yuan; Judd, Julius; Wierbowski, Shayne; Bertolotti, Marta; Nerkar, Mriganka; Jehi, Lara; Drayman, Nir; Nicolaescu, Vlad; Gula, Haley; Tay, Savas; Randall, Glenn; Wang, Peihui; Lis, John T; Feschotte, Cédric; Erzurum, Serpil C; Cheng, Feixiong; Yu, Haiyuan.
  • Zhou Y; Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Liu Y; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
  • Gupta S; Center for Advanced Proteomics, Cornell University, Ithaca, NY, USA.
  • Paramo MI; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
  • Hou Y; Center for Advanced Proteomics, Cornell University, Ithaca, NY, USA.
  • Mao C; Department of Computational Biology, Cornell University, Ithaca, NY, USA.
  • Luo Y; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
  • Judd J; Center for Advanced Proteomics, Cornell University, Ithaca, NY, USA.
  • Wierbowski S; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
  • Bertolotti M; Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Nerkar M; Division of Health and Biomedical Informatics, Department of Preventive Medicine, Northwestern University, Chicago, IL, USA.
  • Jehi L; Division of Health and Biomedical Informatics, Department of Preventive Medicine, Northwestern University, Chicago, IL, USA.
  • Drayman N; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
  • Nicolaescu V; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
  • Gula H; Center for Advanced Proteomics, Cornell University, Ithaca, NY, USA.
  • Tay S; Department of Computational Biology, Cornell University, Ithaca, NY, USA.
  • Randall G; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
  • Wang P; Center for Advanced Proteomics, Cornell University, Ithaca, NY, USA.
  • Lis JT; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
  • Feschotte C; Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Erzurum SC; Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, USA.
  • Cheng F; Department of Microbiology, Ricketts Laboratory, University of Chicago, Chicago, IL, USA.
  • Yu H; Department of Microbiology, Ricketts Laboratory, University of Chicago, Chicago, IL, USA.
Nat Biotechnol ; 2022 Oct 10.
Article in English | MEDLINE | ID: covidwho-2237630
ABSTRACT
Studying viral-host protein-protein interactions can facilitate the discovery of therapies for viral infection. We use high-throughput yeast two-hybrid experiments and mass spectrometry to generate a comprehensive SARS-CoV-2-human protein-protein interactome network consisting of 739 high-confidence binary and co-complex interactions, validating 218 known SARS-CoV-2 host factors and revealing 361 novel ones. Our results show the highest overlap of interaction partners between published datasets and of genes differentially expressed in samples from COVID-19 patients. We identify an interaction between the viral protein ORF3a and the human transcription factor ZNF579, illustrating a direct viral impact on host transcription. We perform network-based screens of >2,900 FDA-approved or investigational drugs and identify 23 with significant network proximity to SARS-CoV-2 host factors. One of these drugs, carvedilol, shows clinical benefits for COVID-19 patients in an electronic health records analysis and antiviral properties in a human lung cell line infected with SARS-CoV-2. Our study demonstrates the value of network systems biology to understand human-virus interactions and provides hits for further research on COVID-19 therapeutics.

Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Journal subject: Biotechnology Year: 2022 Document Type: Article Affiliation country: S41587-022-01474-0

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Journal subject: Biotechnology Year: 2022 Document Type: Article Affiliation country: S41587-022-01474-0