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Aripiprazole as a Candidate Treatment of COVID-19 Identified Through Genomic Analysis

Abstract: Background: 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.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: Frontiers in pharmacology March 2021 Volume 12 Article 646701

Editorial: Frontiers Media

 Fecha de publicación: 02/03/2021

Nº de páginas: 8

Tipo de publicación: Artículo de Revista

 DOI: 10.3389/fphar.2021.646701

ISSN: 1663-9812

Proyecto español: SAF2016- 76046-R and SAF2013-46292-R

Url de la publicación: https://doi.org/10.3389/fphar.2021.646701

Autores/as

CRESPO-FACORRO, BENEDICTO

RUIZ-VEGUILLA, MIGUEL

SÁNCHEZ-HIDALGO, ANA C.

GARRIDO-TORRES, NATHALIA

CISNEROS, JOSE M.

PRIETO, CARLOS

JESUS VICENTE SAINZ MAZA