%0 Journal Article
%A Crespo-Facorro, Benedicto
%A Ruiz-Veguilla, Miguel
%A Vázquez-Bourgon, Javier
%A Sánchez-Hidalgo, Ana C.
%A Garrido-Torres, Nathalia
%A Cisneros, Jose M.
%A Prieto, Carlos
%A Sainz, Jesus
%T Aripiprazole as a Candidate Treatment of COVID-19 Identified Through Genomic Analysis
%D 2021
%U http://hdl.handle.net/10668/4300
%X 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.
%K Psychosis
%K Inflammation
%K Immunology
%K Coronavirus
%K Repurposing drugs
%K Elopiprazole
%K SARS-CoV-2
%K Trastornos psicóticos
%K Inflamación
%K Alergia e inmunología
%K Nuevas indicaciones de medicamentos
%K Inmunidad
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