网络药理学和分子对接分析揭示积雪草苷治疗新型冠状病毒肺炎的作用机制
Network pharmacology and molecular docking analysis reveals the mechanism of asiaticoside on COVID-19.
作者信息
Huang Jia, Zhou Xiaobo, Gong Yiyi, Chen Jun, Yang Yali, Liu Ke
机构信息
Department of Dermatology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Dermatology, Huashan Hospital, Fudan University School of Medicine, Shanghai, China.
出版信息
Ann Transl Med. 2022 Feb;10(4):174. doi: 10.21037/atm-22-51.
BACKGROUND
Asiaticoside (AS) is a saponin extracted from the traditional Chinese herbal medicine , which has the effects of reducing inflammatory infiltration and anti-oxidation in pneumonia and combating pulmonary fibrosis. We hypothesize that AS might have therapeutic potential for the treatment of the coronavirus disease 2019 (COVID-19). With the help of network pharmacology and molecular docking techniques, this study discussed the underlying molecular mechanism of AS in the treatment of COVID-19.
METHODS
The molecular structure of AS was obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) system. The targets of AS were achieved using PharmMapper, SwissTargetPrediction, and the Comparative Toxicogenomics Database (CTD). The targets corresponding to COVID-19 were obtained using GeneCards, Online Mendelian Inheritance in Man (OMIM), and CTD database. Then, a target protein-protein interaction (PPI) network was formed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. A network of AS, COVID-19, and their co-targets was built using Cytoscape. Afterwards, the co-targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Moreover, the predictions of crucial targets were further investigated by performing molecular docking with AS.
RESULTS
A total of 45 core targets of AS were found to be engaged in the pathogenesis of COVID-19. The KEGG enrichment analysis indicated that AS might be protective against COVID-19 through inflammation- and immune-related signaling pathways, including interleukin-17 (IL-17) signaling, T helper 17 (Th17) cell differentiation pathway, Coronavirus disease-COVID-19, MAPK, the PI3K-Akt signaling pathway, and so on. The results of molecular docking showed that AS had a high affinity with those core targets.
CONCLUSIONS
The beneficial effect of AS on COVID-19 might be through regulating multiple immune or inflammation-related targets and signaling pathways.
背景
积雪草苷（AS）是从传统中药中提取的一种皂苷，具有减轻肺炎中的炎症浸润和抗氧化作用以及对抗肺纤维化的作用。我们推测AS可能对2019冠状病毒病（COVID-19）具有治疗潜力。借助网络药理学和分子对接技术，本研究探讨了AS治疗COVID-19的潜在分子机制。
方法
AS的分子结构从中药系统药理学数据库和分析平台（TCMSP）系统中获取。AS的靶点通过PharmMapper、SwissTargetPrediction和比较毒理基因组学数据库（CTD）获得。COVID-19对应的靶点通过GeneCards、人类孟德尔遗传在线（OMIM）和CTD数据库获得。然后，使用基因/蛋白质相互作用检索工具（STRING）数据库形成目标蛋白质-蛋白质相互作用（PPI）网络。使用Cytoscape构建AS、COVID-19及其共同靶点的网络。之后，通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析共同靶点。此外，通过与AS进行分子对接进一步研究关键靶点的预测。
结果
共发现45个AS的核心靶点参与了COVID-19的发病机制。KEGG富集分析表明，AS可能通过炎症和免疫相关信号通路对COVID-19起到保护作用，包括白细胞介素-17（IL-17）信号通路、辅助性T细胞17（Th17）细胞分化途径、冠状病毒病-COVID-19、丝裂原活化蛋白激酶（MAPK）、磷脂酰肌醇-3激酶-蛋白激酶B（PI3K-Akt）信号通路等。分子对接结果表明AS与那些核心靶点具有高亲和力。
结论
AS对COVID-19的有益作用可能是通过调节多个免疫或炎症相关靶点及信号通路实现的。
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