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Updated: Nov 26, 2025
Using Human Differentially Expressed Gene Lists to Perform Downstream Pathway Enrichment Analysis and Target Prioritization
Published on: October 3, 2025
Transcriptomic signatures and repurposing drugs for COVID-19 patients: findings of bioinformatics analyses
Guobing Li1,2, Shasha Ruan3,4, Xiaolu Zhao5
1Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China.
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.
Insights
This study reveals that SARS-CoV-2 infection triggers a cytokine storm, leading to severe COVID-19 pneumonia. Anti-inflammatory drugs like etanercept and baclofen show promise for treating COVID-19 patients.
Area of Science:
- Genomics
- Immunology
- Pharmacology
Background:
- The novel coronavirus (SARS-CoV-2) causes severe COVID-19, necessitating urgent development of effective treatments.
- Current therapeutic options for COVID-19 are limited, highlighting the need for novel drug discovery and repurposing.
Purpose of the Study:
- To investigate the impact of SARS-CoV-2 on host gene expression in lung and blood.
- To identify key molecular mechanisms underlying COVID-19 pathogenesis.
- To discover potential therapeutic agents for COVID-19 through drug repurposing.
Main Methods:
- Transcriptome profiling of lung tissue and blood from COVID-19 patients.
- Differential gene expression analysis to identify affected pathways.
- Weighted gene correlation network analysis (WGCNA) to link gene modules with clinical traits.
- Drug repurposing analysis to screen existing medications.
Main Results:
- SARS-CoV-2 infection induces a "cytokine storm" involving interferon (IFN-α, IFN-β, IFN-γ), tumor necrosis factor (TNF), and interleukin-6 (IL6).
- Immune cells such as neutrophils, macrophages, B cells, and dendritic cells (DC) mediate this inflammatory response.
- Over-activation of the immune system, leading to cytokine release syndrome, is identified as a key pathogenic mechanism in acute COVID-19.
- Drug repurposing analysis identified etanercept (TNFα inhibitor) and baclofen (GABABR agonist) as potent agents reversing the COVID-19 gene signature.
- Other potential treatments include adalimumab, tocilizumab, rituximab, and glucocorticoids, while chloroquine, hydroxychloroquine, and interferons showed limited efficacy.
Conclusions:
- Anti-inflammatory therapies targeting the cytokine storm are promising for COVID-19 treatment.
- Etanercept and baclofen demonstrate significant potential for repurposing in COVID-19 therapy.
- Further controlled clinical trials are essential to validate the efficacy of these candidate drugs against COVID-19.
