Crespo-Facorro, BenedictoRuiz-Veguilla, MiguelVazquez-Bourgon, JavierSanchez-Hidalgo, Ana CGarrido-Torres, NathaliaCisneros, Jose MPrieto, CarlosSainz, Jesus2025-01-072025-01-072021-03-02Crespo-Facorro B, Ruiz-Veguilla M, Vázquez-Bourgon J, Sánchez-Hidalgo AC, Garrido-Torres N, Cisneros JM, et al. Aripiprazole as a Candidate Treatment of COVID-19 Identified Through Genomic Analysis. Front Pharmacol. 2021 Mar 2;12:646701.1663-9812https://hdl.handle.net/10668/27392Antipsychotics 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 nonaffective 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 trialsenAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/SARS-CoV-2coronaviruselopiprazoleimmunologyinflammationpsychosisrepurposing drugsHumansAntipsychotic AgentsphenylpiperazineTranscriptomeDrug RepositioningGene Expression ProfilingImmunityPsychotic DisordersSignal TransductionReceptors, Antigen, B-Cellresearch article33762960open accessPacientesTerapéuticaTrastornos psicóticosEstándares de referenciaPatologíaInmunidadEnzimasEnfermedades inflamatorias del intestino10.3389/fphar.2021.646701PMC7982825https://www.frontiersin.org/articles/10.3389/fphar.2021.646701/pdfhttps://pmc.ncbi.nlm.nih.gov/articles/PMC7982825/pdf