Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, PR China.
Basic Medical College, Guangzhou University of Chinese Medicine, Guangzhou, PR China.
Comput Biol Med. 2022 Nov;150:106134. doi: 10.1016/j.compbiomed.2022.106134. Epub 2022 Sep 22.
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.
新型冠状病毒肺炎疫情对公共卫生构成严重威胁。然而，迄今为止，尚无针对新型冠状病毒肺炎的有效药物。新型冠状病毒肺炎患者的转录组变化和与 Th2 细胞相关的关键基因尚未报道。这些基因在宿主与 SARS-CoV-2 的相互作用中发挥着重要作用，可能成为有前途的靶点。我们使用 xCell 算法和加权基因共表达网络分析（WGCNA）分析了五个与新型冠状病毒肺炎相关的 GEO 数据集（GSE157103、GSE152641、GSE171110、GSE152418 和 GSE179627）。结果表明，5 个与新型冠状病毒肺炎和 Th2 细胞富集水平密切相关的模块化基因，包括紫色、蓝色、粉色、棕褐色和绿松石色，与差异表达基因（DEGs）相交，并获得了 648 个共享基因。GO 和 KEGG 通路富集分析显示，它们富集于病毒感染后的细胞增殖、分化和免疫反应。最显著富集的通路涉及病毒生命周期的调节。三个关键基因，即 CCNB1、BUB1 和 UBE2C，可能阐明与 Th2 细胞相关的新型冠状病毒肺炎的发病机制。使用 cMAP 数据库确定了 11 种候选药物，这些药物可下调三个关键基因，使用分子对接方法证实了这些药物对三个关键基因具有很强的结合能。BUB1、CCNB1 和 UBE2C 被确定为新型冠状病毒肺炎的关键基因，可能成为有前途的治疗靶点。
