Integrative analysis of functional genomic screening and clinical data identifies a protective role for spironolactone in severe COVID-19.
Cell Rep Methods
; 3(7): 100503, 2023 07 24.
Article
em En
| MEDLINE
| ID: mdl-37529368
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
COVID-19
Tipo de estudo:
Diagnostic_studies
/
Guideline
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Screening_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article