Crespo-Facorro, BenedictoRuiz-Veguilla, MiguelVázquez-Bourgon, JavierSánchez-Hidalgo, Ana C.Garrido-Torres, NathaliaCisneros, Jose M.Prieto, CarlosSainz, Jesus2022-10-312022-10-312021-03-02Crespo-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;12:646701http://hdl.handle.net/10668/4300Background: 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/PsychosisInflammationImmunologyCoronavirusRepurposing drugsElopiprazoleSARS-CoV-2Trastornos psicóticosInflamaciónAlergia e inmunologíaNuevas indicaciones de medicamentosInmunidadMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Central Nervous System Depressants::Tranquilizing Agents::Antipsychotic AgentsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression::Transcription, Genetic::TranscriptomeMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Drug Discovery::Drug RepositioningMedical Subject Headings::Psychiatry and Psychology::Mental Disorders::Schizophrenia and Disorders with Psychotic Features::Psychotic DisordersMedical Subject Headings::Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::CytokinesMedical Subject Headings::Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Inflammatory Bowel DiseasesMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell DifferentiationMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Signal TransductionMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Antigen::Receptors, Antigen, B-CellMedical Subject Headings::Phenomena and Processes::Immune System Phenomena::Immunityresearch article33762960open access10.3389/fphar.2021.6467011663-9812PMC7982825