RT Journal Article T1 Aripiprazole as a Candidate Treatment of COVID-19 Identified Through Genomic Analysis. A1 Crespo-Facorro, Benedicto A1 Ruiz-Veguilla, Miguel A1 Vazquez-Bourgon, Javier A1 Sanchez-Hidalgo, Ana C A1 Garrido-Torres, Nathalia A1 Cisneros, Jose M A1 Prieto, Carlos A1 Sainz, Jesus K1 SARS-CoV-2 K1 coronavirus K1 elopiprazole K1 immunology K1 inflammation K1 psychosis K1 repurposing drugs AB 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 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 trials PB Frontiers Research Foundation SN 1663-9812 YR 2021 FD 2021-03-02 LK https://hdl.handle.net/10668/27392 UL https://hdl.handle.net/10668/27392 LA en NO Crespo-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. DS RISalud RD Apr 5, 2025