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Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Cell 2021 ; 184 (1): 76-91.e13 Nephropedia Template TP
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]