Fang Yanhua, Zhang Lingling, Wang Zhe, Wang Ruoyu, Liang Shanshan
The Key Laboratory of Biomarker High Throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China.
Oncology Department, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China.
Front Pharmacol. 2022 Aug 11;13:969709. doi: 10.3389/fphar.2022.969709. eCollection 2022.
Reports of hepatitis in children during the coronavirus disease 2019 (COVID-19) pandemic garnered worldwide attention. The most probable culprits are adenovirus and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). At present, the optimal symptomatic treatment consists of a combination of anti-COVID-19 and hepatitis symptom alleviators. Schisandrin B (SchB) has been known to have liver-protective properties for a long time, whereas anti-COVID-19 properties only recently have been discovered. In the case of COVID-19 with hepatitis of unknown origin, we used network pharmacology to explore the symptomatic therapy and protective effects of SchB. The most probable protein targets of SchB were predicted in the SwissTargetPrediction database. The GeneCards, National Center for Biotechnology Information, and Online Mendelian Inheritance in Man databases were used to compile information on the diseases hepatitis, adenovirus, and SARS-CoV-2. Following the use of a Venn diagram viewer to identify intersection genes, we constructed a protein-protein interaction network and identified the core genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment, as well as molecular docking, were employed to highlight the mechanisms of SchB on hepatitis. SchB contains 27 targets on adenovirus_hepatitis and 16 targets on SARS-CoV-2_hepatitis, with 12 shared genes. Both target populations clustered in viral infection and cancer pathways, as well as in processes such as kinase activity phosphatase, cell adhesion, and ATPase binding. These genes might be closely related to liver damage and membrane binding from adenovirus or SARS-CoV-2 infections. In addition, epidermal growth factor receptor, HSP90AA1, and MAPK1 were among the top five targets of both SchB SARS-CoV-2 hepatitis and SchB adenovirus hepatitis. SchB may target common protective targets and mechanisms against acute hepatitis caused by adenovirus or by SARS-CoV-2 in children during the COVID-19 pandemic. These findings indicate SchB's potential as a treatment for hepatitis of unknown origin.
2019年冠状病毒病（COVID-19）大流行期间儿童肝炎的报告引起了全球关注。最可能的病原体是腺病毒和严重急性呼吸综合征冠状病毒2（SARS-CoV-2）。目前，最佳的对症治疗包括抗COVID-19药物和缓解肝炎症状药物的联合使用。五味子醇甲（SchB）长期以来已知具有肝脏保护特性，而其抗COVID-19特性直到最近才被发现。对于病因不明的COVID-19合并肝炎病例，我们使用网络药理学来探索SchB的对症治疗和保护作用。在SwissTargetPrediction数据库中预测了SchB最可能的蛋白质靶点。利用基因卡片数据库、美国国立生物技术信息中心数据库和人类孟德尔遗传在线数据库收集有关肝炎、腺病毒和SARS-CoV-2疾病的信息。在使用维恩图查看器识别交集基因后，我们构建了蛋白质-蛋白质相互作用网络并确定了核心基因。采用基因本体论和京都基因与基因组百科全书富集分析以及分子对接技术来突出SchB对肝炎的作用机制。SchB在腺病毒相关性肝炎中有27个靶点，在SARS-CoV-2相关性肝炎中有16个靶点，其中有12个共享基因。两个靶点群体都聚集在病毒感染和癌症通路以及激酶活性磷酸酶、细胞黏附、ATP酶结合等过程中。这些基因可能与腺病毒或SARS-CoV-2感染导致的肝损伤和膜结合密切相关。此外，表皮生长因子受体、热休克蛋白90α家族成员1（HSP90AA1）和丝裂原活化蛋白激酶1（MAPK1）是SchB治疗SARS-CoV-2相关性肝炎和SchB治疗腺病毒相关性肝炎的前五大靶点。SchB可能针对COVID-19大流行期间儿童由腺病毒或SARS-CoV-2引起的急性肝炎的共同保护靶点和机制。这些发现表明SchB在治疗病因不明的肝炎方面具有潜力。
