{"doi":"10.1016/j.crmeth.2023.100503","title":"Integrative analysis of functional genomic screening and clinical data identifies a protective role for spironolactone in severe COVID-19","abstract":"We demonstrate that integrative analysis of CRISPR screening datasets enables network-based prioritization of prescription drugs modulating viral entry in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by developing a network-based approach called Rapid proXimity Guidance for Repurposing Investigational Drugs (RxGRID). We use our results to guide a propensity-score-matched, retrospective cohort study of 64,349 COVID-19 patients, showing that a top candidate drug, spironolactone, is associated with improved clinical prognosis, measured by intensive care unit (ICU) admission and mechanical ventilation rates. Finally, we show that spironolactone exerts a dose-dependent inhibitory effect on viral entry in human lung epithelial cells. Our RxGRID method presents a computational framework, implemented as an open-source software package, enabling genomics researchers to identify drugs likely to modulate a molecular phenotype of interest based on high-throughput screening data. Our results, derived from this method and supported by experimental and clinical analysis, add additional supporting evidence for a potential protective role of the potassium-sparing diuretic spironolactone in severe COVID-19.","journal":"Cell Reports Methods","year":2023,"id":374834,"datarank":0.2615012017563408,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.020085514891225686,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.020085514891225686,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":3,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9599,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":983757,"name":"Adrienne Sarah Kline","orcid":null,"position":1,"is_corresponding":false},{"id":471184,"name":"Chengkun Wang","orcid":"0000-0002-2505-7295","position":2,"is_corresponding":false},{"id":854309,"name":"Yuanhao Qu","orcid":"0000-0002-7574-259X","position":3,"is_corresponding":false},{"id":227953,"name":"James Zengel","orcid":"0000-0003-3153-3603","position":4,"is_corresponding":false},{"id":227957,"name":"Jan E. Carette","orcid":"0000-0002-5187-8070","position":5,"is_corresponding":false},{"id":854310,"name":"Mengdi Wang","orcid":"0000-0002-2101-9507","position":6,"is_corresponding":false},{"id":3452,"name":"Russ B. Altman","orcid":"0000-0003-3859-2905","position":7,"is_corresponding":false},{"id":58247,"name":"Yuan Luo","orcid":"0000-0003-0195-7456","position":8,"is_corresponding":false},{"id":15696,"name":"Le Cong","orcid":"0000-0003-4725-8714","position":9,"is_corresponding":false},{"id":946094,"name":"Henry C. Cousins","orcid":"0000-0002-8694-0604","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:16:15.380731Z","pmid":"37529368","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}