{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE335nnn/GSE335103/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Homo sapiens"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE335103"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Genome-wide Screening Identifies Unique Host-Directed Drugs and Pro-viral Signalling Pathways for SARS-CoV-2","description":"SARS-CoV-2 is a positive-sense RNA virus that was responsible for the devastating COVID-19 pandemic. Although the current disease burden is less severe, there are limited treatment options, and a looming threat of the emergence of variants and future pandemics. To address these challenges, we performed genome-wide CRISPR knockout screens in a novel human lung cell line NCI-H23ACE2, as well as in HEK293TACE2 cells, with SARS-CoV-2 Wuhan strain, and identified several host-dependency factors including NRAS, KAT5, HTR3E and GNL3L. Drugs targeting some of these dependency factors, donepezil, dH-ergocristine, trametinib and sorafenib, showed effective pan-coronaviral inhibition in cell lines. Trametinib also showed inhibition of SARS-CoV-2 Delta variant in primary human airway tissue model (ALI). We also demonstrate that SARS-CoV-2 inhibits IFN-β induction through an NRAS/Raf/MEK/ERK signaling pathway dependent mechanism. Our study highlights the efficiency of a bilateral approach of gene silencing and antiviral screening to identify host-dependency factors and effective antivirals.","dates":{"publication":"2026/06/16"},"accession":"GSE335103","cross_references":{"GSM":["GSM9805860","GSM9805861","GSM9805852","GSM9805863","GSM9805864","GSM9805865","GSM9805854","GSM9805855","GSM9805866","GSM9805856","GSM9805858","GSM9805859"],"GPL":["20301"],"GSE":["335103"],"taxon":["Homo sapiens"]}}