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dc.creatorCrespo Facorro, Benedictoes
dc.creatorRuiz Veguilla, Migueles
dc.creatorVázquez-Bourgon, Javieres
dc.creatorSánchez-Hidalgo, Ana C.es
dc.creatorGarrido-Torres, Nathaliaes
dc.creatorCisneros, José Migueles
dc.creatorPrieto, Carloses
dc.creatorSainz, Jesúses
dc.date.accessioned2022-10-14T10:41:42Z
dc.date.available2022-10-14T10:41:42Z
dc.date.issued2021
dc.identifier.citationCrespo Facorro, B., Ruiz Veguilla, M., Vázquez-Bourgon, J., Sánchez-Hidalgo, A.C., Garrido-Torres, N., Cisneros Herreros, J.M.,...,Sainz, J. (2021). Aripiprazole as a candidate treatment of COVID-19 identified through genomic analysis. Frontiers in Pharmacology, 12. https://doi.org/10.3389/fphar.2021.646701.
dc.identifier.issn1663-9812es
dc.identifier.urihttps://hdl.handle.net/11441/137907
dc.description.abstractBackground: Antipsychotics modulate expression of inflammatory cytokines and inducible inflammatory enzymes. Elopiprazole (a phenylpiperazine antipsychotic drug in phase 1) has been characterized as a therapeutic drug to treat SARS-CoV-2 infection in a repurposing study. We aim to investigate the potential effects of aripiprazole (an FDA approved phenylpiperazine) on COVID-19-related immunological parameters. Methods: Differential gene expression profiles of non-COVID-19 vs. COVID-19 RNA-Seq samples (CRA002390 project in GSA database) and drug-naïve patients with non-affective psychosis at baseline and after three months of aripiprazole treatment were identified. An integrative transcriptomic analyses of aripiprazole effects on differentially expressed genes in COVID-19 patients was performed. Findings: 82 out the 377 genes (21.7%) with expression significantly altered by aripiprazole have also their expression altered in COVID-19 patients and in 93.9% of these genes their expression is reverted by aripiprazole. The number of common genes with expression altered in both analyses is significantly higher than expected (Fisher’s Exact Test, two tail; p value = 3.2e-11). 11 KEGG pathways were significantly enriched with genes with altered expression both in COVID-19 patients and aripiprazole medicated non-affective psychosis patients (p adj<0.05). The most significant pathways were associated to immune responses and mechanisms of hyperinflammation-driven pathology (i.e.,“inflammatory bowel disease (IBD)” (the most significant pathway with a p adj of 0.00021), “Th1 and Th2 cell differentiation” and “B cell receptor signaling pathway”) that have been also associated with COVID19 clinical outcome. Interpretation: This exploratory investigation may provide further support to the notion that a protective effect is exerted by aripiprazole (phenylpiperazine) by modulating the expression of genes that have shown to be altered in COVID-19 patients. Along with many ongoing studies and clinical trials, repurposing available medications could be of use in countering SARS-CoV-2 infection, but require further studies and trials. © Copyright © 2021 Crespo-Facorro, Ruiz-Veguilla, Vázquez-Bourgon, Sánchez-Hidalgo, Garrido-Torres, Cisneros, Prieto and Sainz.es
dc.formatapplication/pdfes
dc.language.isoenges
dc.publisherFrontiers Media SAes
dc.relation.ispartofFrontiers in Pharmacology, 12.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectCoronaviruses
dc.subjectElopiprazolees
dc.subjectImmunologyes
dc.subjectInflammationes
dc.subjectPsychosises
dc.subjectRepurposing drugses
dc.subjectSARS-CoV-2es
dc.titleAripiprazole as a candidate treatment of COVID-19 identified through genomic analysises
dc.typeinfo:eu-repo/semantics/articlees
dcterms.identifierhttps://ror.org/03yxnpp24
dc.type.versioninfo:eu-repo/semantics/publishedVersiones
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Psiquiatríaes
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Medicinaes
dc.relation.projectIDSAF2016- 76046-Res
dc.relation.projectIDSAF2013-46292-Res
dc.relation.publisherversionhttps://www.frontiersin.org/articles/10.3389/fphar.2021.646701/fulles
dc.identifier.doi10.3389/fphar.2021.646701es
dc.journaltitleFrontiers in Pharmacologyes
dc.publication.volumen12es
dc.contributor.funderMinisterio de Economía y Competitividad (MINECO). Españaes
dc.contributor.funderEuropean Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)es

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