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10.1016/j.cell.2020.10.028

http://scihub22266oqcxt.onion/10.1016/j.cell.2020.10.028
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33147444!7574718!33147444
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suck abstract from ncbi


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pmid33147444      Cell 2021 ; 184 (1): 76-91.e13
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  • Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection #MMPMID33147444
  • Wei J; Alfajaro MM; DeWeirdt PC; Hanna RE; Lu-Culligan WJ; Cai WL; Strine MS; Zhang SM; Graziano VR; Schmitz CO; Chen JS; Mankowski MC; Filler RB; Ravindra NG; Gasque V; de Miguel FJ; Patil A; Chen H; Oguntuyo KY; Abriola L; Surovtseva YV; Orchard RC; Lee B; Lindenbach BD; Politi K; van Dijk D; Kadoch C; Simon MD; Yan Q; Doench JG; Wilen CB
  • Cell 2021[Jan]; 184 (1): 76-91.e13 PMID33147444show ga
  • Identification of host genes essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may reveal novel therapeutic targets and inform our understanding of coronavirus disease 2019 (COVID-19) pathogenesis. Here we performed genome-wide CRISPR screens in Vero-E6 cells with SARS-CoV-2, Middle East respiratory syndrome CoV (MERS-CoV), bat CoV HKU5 expressing the SARS-CoV-1 spike, and vesicular stomatitis virus (VSV) expressing the SARS-CoV-2 spike. We identified known SARS-CoV-2 host factors, including the receptor ACE2 and protease Cathepsin L. We additionally discovered pro-viral genes and pathways, including HMGB1 and the SWI/SNF chromatin remodeling complex, that are SARS lineage and pan-coronavirus specific, respectively. We show that HMGB1 regulates ACE2 expression and is critical for entry of SARS-CoV-2, SARS-CoV-1, and NL63. We also show that small-molecule antagonists of identified gene products inhibited SARS-CoV-2 infection in monkey and human cells, demonstrating the conserved role of these genetic hits across species. This identifies potential therapeutic targets for SARS-CoV-2 and reveals SARS lineage-specific and pan-CoV host factors that regulate susceptibility to highly pathogenic CoVs.
  • |*Genome-Wide Association Study[MESH]
  • |*Host-Pathogen Interactions/drug effects[MESH]
  • |Angiotensin-Converting Enzyme 2/metabolism[MESH]
  • |Animals[MESH]
  • |COVID-19/immunology/virology[MESH]
  • |Cell Line[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Clustered Regularly Interspaced Short Palindromic Repeats[MESH]
  • |Coronavirus Infections/drug therapy/*genetics/immunology[MESH]
  • |Coronavirus/classification[MESH]
  • |Gene Knockout Techniques[MESH]
  • |Gene Regulatory Networks[MESH]
  • |HEK293 Cells[MESH]
  • |HMGB1 Protein/genetics/metabolism[MESH]
  • |Humans[MESH]
  • |SARS-CoV-2/*physiology[MESH]
  • |Vero Cells[MESH]


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