Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Mar 2:12:646701.
doi: 10.3389/fphar.2021.646701. eCollection 2021.

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

Benedicto Crespo-Facorro  1   2 , Miguel Ruiz-Veguilla  1   2 , Javier Vázquez-Bourgon  2   3   4 , Ana C Sánchez-Hidalgo  2   5 , Nathalia Garrido-Torres  1 , Jose M Cisneros  6   7 , Carlos Prieto  8 , Jesus Sainz  9
Affiliations

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

Benedicto Crespo-Facorro et al. Front Pharmacol. .

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.

Keywords: SARS-CoV-2; coronavirus; elopiprazole; immunology; inflammation; psychosis; repurposing drugs.

PubMed Disclaimer

Conflict of interest statement

BC-F has received unrestricted research funding from Instituto de Salud Carlos III, MINECO, Gobierno de Cantabria, Spanish Network for Research in Mental Health (CIBERSAM), from the seventh European Union Framework Program and Lundbeck. He has also received honoraria for his participation as a consultant and/or as a speaker at educational events from Janssen Johnson & Johnson, Mylan, Lundbeck, and Otsuka Pharmaceuticals. MR-V has received unrestricted research funding from Instituto de Salud Carlos III. He has also received honoraria for his participation as a consultant and/or as a speaker at educational events from Janssen, Lundbeck, and Otsuka Pharmaceuticals. JV-B has received unrestricted research funding from Instituto de Investigación Marqués de Valdecilla (IDIVAL). He has also received honoraria for his participation as a consultant and/or as a speaker at educational events from Janssen-Cilag and Lundbeck. JC has received honoraria as a speaker from Novartis, Astellas Pharma, Pfizer, MSD, Janssen Pharmaceuticals, and AstraZeneca, outside the submitted work. He has also received report grants from Instituto de Salud Carlos III, Spanish Government, co-financed by the European Development Regional Fund “A way to achieve Europe,” during the conduct of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Number of genes with expression altered in Wuhan sample (COVID-19) and PAFIP sample (aripiprazole-treated).
FIGURE 2
FIGURE 2
Chemical structures of two phenypiperazines with antipsychotic effects: elopiprazole and aripiprazole.
See this image and copyright information in PMC

References

    1. Bhaskar S., Sinha A., Banach M., Mittoo S., Weissert R., Kass J. S., et al. (2020). Cytokine storm in COVID-19-Immunopathological mechanisms, clinical considerations, and therapeutic approaches: the REPROGRAM consortium position paper. Front. Immunol. 11, 1648. 10.3389/fimmu.2020.01648 - DOI - PMC - PubMed
    1. Bouadma L., Wiedemann A., Patrier J., Surénaud M., Wicky P. H., Foucat E., et al. (2020). Immune alterations in a patient with SARS-CoV-2-related acute respiratory distress syndrome. J. Clin. Immunol. 40 (8), 1082–1092. 10.1007/s10875-020-00839-x - DOI - PMC - PubMed
    1. Canal-Rivero M., Barragán R. C., García A. R., Garrido-Torres N., Crespo-Facorro B., Ruiz-Veguilla M. (2021). Lower risk of SARS-CoV2 infection in individuals with severe mental disorders on antipsychotic treatment: A retrospective epidemiological study in a representative Spanish population. Schizophrenia Res. 229, 53–54. 10.1016/j.schres.2021.02.002 - DOI - PMC - PubMed
    1. Chen G., Wu D., Guo W., Cao Y., Huang D., Wang H., et al. (2020). Clinical and immunological features of severe and moderate coronavirus disease 2019. J. Clin. Invest. 130 (5), 2620–2629. 10.1172/JCI137244 - DOI - PMC - PubMed
    1. Crespo-Facorro B., Ortiz-Garcia de la Foz V., Suarez-Pinilla P., Valdizan E. M., Pérez-Iglesias R., Amado-Señaris J. A., et al. (2017). Effects of aripiprazole, quetiapine and ziprasidone on plasma prolactin levels in individuals with first episode nonaffective psychosis: analysis of a randomized open-label 1year study. Schizophr. Res. 189, 134–141. 10.1016/j.schres.2017.01.046 - DOI - PubMed