Ma Xiao, Huang Tengda, Song Yujia, Pan Hongyuan, Du Ao, Zhou Xinyi, Zeng Yong, Yuan Kefei
Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
PLoS One. 2025 May 23;20(5):e0323708. doi: 10.1371/journal.pone.0323708. eCollection 2025.
The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents a significant global public health threat. Concurrently, hepatitis B virus (HBV) remains a significant public health challenge. While previous studies have indicated an association between COVID-19 and chronic hepatitis B, the common underlying pathogenesis of these diseases remains incompletely understood.
To investigate the shared molecular mechanisms between chronic HBV infection and COVID-19, a comprehensive investigation was conducted using bioinformatics and systems biology. Specifically, we utilized RNA-seq datasets (GSE196822 and GSE83148) to identify differentially expressed genes (DEGs) associated with both SARS-CoV-2 and HBV infection. Subsequently, these common DEGs were utilized to identify shared pathways, hub genes, transcriptional regulatory networks, and potential drugs. The differential expression of hub genes in both COVID-19 and HBV was verified using the GSE171110 and GSE94660 datasets, respectively.
From the 106 shared DEGs identified, immune-related pathways were found to play a role in the development and progression of chronic hepatitis B and COVID-19. Protein-protein interaction (PPI) network analysis revealed 8 hub genes: CDK1, E2F7, E2F8, TYMS, KIF20A, CENPE, TPX2, HMMR, CD8A, GZMA. In the validation set, the expression of hub genes was statistically significant in both the COVID-19 group and the HBV group compared with the healthy control group. Transcriptional regulatory network analysis identified 155 microRNAs (miRNAs) and 43 transcription factors (TFs) as potential regulatory signals. Notably, we identified potential therapeutic drugs for HBV chronic infection and COVID-19, including progesterone, estradiol, dasatinib, aspirin, etoposide, irinotecan hydrochloride, phorbol 12-myristate 13-acetate, lucanthone, calcitriol.
This research elucidates potential molecular targets, signaling pathways, and promising small molecule compounds that could aid in the treatment of chronic HBV infection and COVID-19.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的2019冠状病毒病（COVID-19）大流行对全球公共卫生构成了重大威胁。同时，乙型肝炎病毒（HBV）仍然是一项重大的公共卫生挑战。虽然先前的研究表明COVID-19与慢性乙型肝炎之间存在关联，但这些疾病共同的潜在发病机制仍未完全了解。
为了研究慢性HBV感染与COVID-19之间共同的分子机制，利用生物信息学和系统生物学进行了全面调查。具体而言，我们利用RNA测序数据集（GSE196822和GSE83148）来鉴定与SARS-CoV-2和HBV感染均相关的差异表达基因（DEG）。随后，利用这些共同的DEG来鉴定共享途径、枢纽基因、转录调控网络和潜在药物。分别使用GSE171110和GSE94660数据集验证了COVID-19和HBV中枢纽基因的差异表达。
从鉴定出的106个共同DEG中发现，免疫相关途径在慢性乙型肝炎和COVID-19的发生发展中起作用。蛋白质-蛋白质相互作用（PPI）网络分析揭示了8个枢纽基因：细胞周期蛋白依赖性激酶1（CDK1）、E2F转录因子7（E2F7）、E2F转录因子8（E2F8）、胸苷酸合成酶（TYMS）、驱动蛋白家族成员20A（KIF20A）、着丝粒蛋白E（CENPE）、肿瘤蛋白p53结合蛋白2（TPX2）、透明质酸介导的运动受体（HMMR）、细胞毒性T淋巴细胞相关蛋白8A（CD8A）、颗粒酶A（GZMA）。在验证集中，与健康对照组相比，枢纽基因的表达在COVID-19组和HBV组中均具有统计学意义。转录调控网络分析确定了155个微小RNA（miRNA）和43个转录因子（TF）作为潜在的调控信号。值得注意的是，我们鉴定出了用于慢性HBV感染和COVID-19的潜在治疗药物，包括孕酮、雌二醇、达沙替尼、阿司匹林、依托泊苷、盐酸伊立替康、佛波醇12-肉豆蔻酸酯13-乙酸酯、卢卡酮、骨化三醇。
本研究阐明了可能有助于治疗慢性HBV感染和COVID-19的潜在分子靶点、信号通路和有前景的小分子化合物。
