Aripiprazole as a candidate treatment of COVID-19 identified through genomic analysis

Background: Antipsychotics suppress 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 COVID19-related immunological parameters. Methods: Differential gene expression profiles of non-COVID versus COVID RNA-Seq samples (CRA002390 project in GSA database) and drug-naive patients with psychosis at baseline and after three months of aripiprazole treatment was identified. An integrative analysis between COVID and aripiprazole immunomodulatory antagonist effects 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 (Fisher9s 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 schizophrenia patients (P adj<0.05). The most significant pathways were associated to the immune system such as the 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, all three related to the defense against infections. Interpretation: This exploratory investigation may provide further support to the notion that protective effect is exerted by phenylpiperazine by modulating the immunological dysregulation associated to COVID-19. 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.