Transcriptomic Signatures and Repurposing Drugs for COVID-19 Patients: Findings of Bioinformatics Analyses

29 Pages Posted: 26 Jun 2020 Last revised: 14 Dec 2020

See all articles by Guobing Li

Guobing Li

University of Michigan at Ann Arbor

Shasha Ruan

Wuhan University

Xiaolu Zhao

University of Michigan at Ann Arbor

Qi Liu

Harvard University - Harvard Medical School

Yali Dou

University of Michigan at Ann Arbor - Department of Pathology

Fengbiao Mao

University of Michigan at Ann Arbor

Date Written: June 23, 2020

Abstract

The novel coronavirus SARS-CoV-2 is damaging the world’s social and economic fabrics seriously. Effective drugs are urgently needed to decrease the high mortality rate of COVID-19 patients. Unfortunately, effective antiviral drugs or vaccines are currently unavailable. Herein, we systematically evaluated the effect of SARS-CoV-2 on gene expression of both lung tissue and blood from COVID-19 patients using transcriptome profiling. Differential gene expression analysis revealed potential core mechanism of COVID-19-induced pneumonia in which IFN-α, IFN-β, IFN-γ, TNF and IL6 triggered cytokine storm mediated by neutrophil, macrophage, B and DC cells. Weighted gene correlation network analysis identified two gene modules that are highly correlated with clinical traits of COVID-19 patients, and confirmed that over-activation of immune system-mediated cytokine release syndrome is the underlying pathogenic mechanism for acute phase of COVID-19 infection. It suggested that anti-inflammatory therapies may be promising regimens for COVID-19 patients. Furthermore, drug repurposing analysis of thousands of drugs revealed that TNFα inhibitor etanercept and γ-aminobutyric acid-B receptor (GABABR) agonist baclofen showed most significant reversal power to COVID-19 gene signature, so we are highly optimistic about their clinical use for COVID-19 treatment. In addition, our results suggested that adalimumab, tocilizumab, rituximab and glucocorticoids may also have beneficial effects in restoring normal transcriptome, but not chloroquine, hydroxychloroquine or interferons. Controlled clinical trials of these candidate drugs are needed in search of effective COVID-19 treatment in current crisis.

Note: Funding: No specific grant from any funding agency for this study.

Conflict of Interest: The authors report no conflicts of interest in this work.

Keywords: COVID-19; SARS-CoV-2; Transcriptomic signatures; Immunomodulatory treatments

Suggested Citation

Li, Guobing and Ruan, Shasha and Zhao, Xiaolu and Liu, Qi and Dou, Yali and Mao, Fengbiao, Transcriptomic Signatures and Repurposing Drugs for COVID-19 Patients: Findings of Bioinformatics Analyses (June 23, 2020). Available at SSRN: https://ssrn.com/abstract=3620818 or http://dx.doi.org/10.2139/ssrn.3620818

Guobing Li

University of Michigan at Ann Arbor ( email )

Shasha Ruan

Wuhan University ( email )

Wuhan
China

Xiaolu Zhao

University of Michigan at Ann Arbor ( email )

Qi Liu

Harvard University - Harvard Medical School ( email )

25 Shattuck St
Boston, MA 02115
United States

Yali Dou

University of Michigan at Ann Arbor - Department of Pathology

Ann Arbor, MI 48109,
United States

Fengbiao Mao (Contact Author)

University of Michigan at Ann Arbor ( email )

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