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Analysis and identification of potential type II helper T cell (Th2)-Related key genes and therapeutic agents for
Qiying Jin1, Wanxi Li1, Wendi Yu1
1Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, PR China.
Abstract:
COVID-19 pandemic poses a severe threat to public health. However, so far, there are no effective drugs for COVID-19. Transcriptomic changes and key genes related to Th2 cells in COVID-19 have not been reported. These genes play an important role in host interactions with SARS-COV-2 and may be used as promising target. We analyzed five COVID-19-associated GEO datasets (GSE157103, GSE152641, GSE171110, GSE152418, and GSE179627) using the xCell algorithm and weighted gene co-expression network analysis (WGCNA). Results showed that 5 closely correlated modular genes to COVID-19 and Th2 cell enrichment levels, including purple, blue, pink, tan and turquoise, were intersected with differentially expressed genes (DEGs) and 648 shared genes were obtained. GO and KEGG pathway enrichment analyses revealed that they were enriched in cell proliferation, differentiation, and immune responses after virus infection. The most significantly enriched pathway involved the regulation of viral life cycle. Three key genes, namely CCNB1, BUB1, and UBE2C, may clarify the pathogenesis of COVID-19 associated with Th2 cells. 11 drug candidates were identified that could down-regulate three key genes using the cMAP database and demonstrated strong drugs binding energies aganist the three keygenes using molecular docking methods. BUB1, CCNB1 and UBE2C were identified key genes for COVID-19 and could be promising therapeutic targets.
Insights
Researchers identified key genes (CCNB1, BUB1, UBE2C) linked to Th2 cells in COVID-19 pathogenesis. These genes offer potential therapeutic targets, with 11 drug candidates identified for further investigation in treating the viral infection.
Area of Science:
- Immunology
- Virology
- Genomics
Background:
- The COVID-19 pandemic presents a significant global health challenge with no currently effective antiviral drugs.
- Understanding the host's transcriptomic response, particularly involving T helper 2 (Th2) cells, is crucial for identifying therapeutic targets against SARS-CoV-2.
Purpose of the Study:
- To identify key genes associated with Th2 cell responses in COVID-19 patients.
- To explore potential therapeutic targets and drug candidates for COVID-19 treatment based on transcriptomic data.
Main Methods:
- Analysis of five COVID-19-related Gene Expression Omnibus (GEO) datasets using xCell and weighted gene co-expression network analysis (WGCNA).
- Intersection of co-expression modules with differentially expressed genes (DEGs) to identify shared genes.
- Gene Ontology (GO) and KEGG pathway enrichment analyses were performed.
- Identification of drug candidates using the cMAP database and molecular docking.
Main Results:
- 648 shared genes were identified, significantly enriched in pathways related to cell proliferation, differentiation, and immune responses to viral infection, including viral life cycle regulation.
- Three key genes—CCNB1, BUB1, and UBE2C—were highlighted for their potential role in COVID-19 pathogenesis associated with Th2 cells.
- Eleven potential drug candidates were identified that could down-regulate these key genes, showing strong binding affinities.
Conclusions:
- CCNB1, BUB1, and UBE2C are identified as critical genes in COVID-19 pathogenesis linked to Th2 cell activity.
- These genes represent promising therapeutic targets for developing new COVID-19 treatments.
- The identified drug candidates warrant further investigation for their efficacy in down-regulating these target genes.
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