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 Vázquez-Bourgon, Javier
A1 Sánchez-Hidalgo, Ana C.
A1 Garrido-Torres, Nathalia
A1 Cisneros, Jose M.
A1 Prieto, Carlos
A1 Sainz, Jesus
K1 Psychosis
K1 Inflammation
K1 Immunology
K1 Coronavirus
K1 Repurposing drugs
K1 Elopiprazole
K1 SARS-CoV-2
K1 Trastornos psicóticos
K1 Inflamación
K1 Alergia e inmunología
K1 Nuevas indicaciones de medicamentos
K1 Inmunidad
AB 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.
PB Frontiers
YR 2021
FD 2021-03-02
LK http://hdl.handle.net/10668/4300
UL http://hdl.handle.net/10668/4300
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 20, 2025