抗白细胞介素6受体的活性成分虚拟筛选及其核心中药干预新冠肺炎的网络药理学机制探讨  

Virtual Screening of Active Components of Interleukin-6 Receptor and Investigation of the Network Pharmacological Mechanism of the Core Traditional Chinese Medicine Against COVID-19

作　　者：吴坚 张锡洪[1] 徐文坚 WU Jian;ZHANG Xihong;XU Wenjian(Shantou Central Hospital,Shantou,Guangdong,China 515031;Xiaolan People's Hospital of Zhongshan,Zhongshan,Guangdong,China 528400)

机构地区：[1]广东省汕头市中心医院,广东汕头515031 [2]广东省中山市小榄人民医院,广东中山528400

出　　处：《中国药业》2021年第21期35-43,共9页China Pharmaceuticals

摘　　要：目的筛选白细胞介素6受体(IL-6R)的天然小分子抑制剂,预测含有该类成分最多的中药干预新型冠状病毒肺炎(COVID-19)的作用机制。方法利用ADME-Lipinski规律筛选IL-6R的活性成分,以IL-6R为靶点,运用Autodock Vina软件和Python脚本对IL-6R的天然小分子抑制剂进行高通量分子对接,获得具有潜在IL-6R抑制活性的天然小分子化合物及含有该类成分的核心中药;构建"成分-靶点-通路"网络,预测核心中药干预COVID-19的作用机制。结果获得口服生物利用度(OB)≥30%、类药性(DL)≥0.18的成分1 511个,涉及372种中药。其中,芝麻素与IL-6R对接最好,木犀草素来源最广,甘草含抗IL-6R活性成分最多。网络药理学研究结果显示,甘草抗COVID-19的潜在靶点共16个,并富集获得了7条与COVID-19发生、发展密切相关的生物通路,包括低氧诱导因子1、血管内皮生长因子、血小板活化、肿瘤坏死因子、磷脂酰肌醇3-激酶-苏氨酸蛋白激酶、白细胞介素17、Toll样受体等,上述通路主要涉及免疫调节、炎性干预、氧化应激、抗凝与凝血系统调控等方面。结论芝麻素、木犀草素和甘草对COVID-19的发生、发展具有多途径的潜在干预能力,可为抗COVID-19的新药开发提供理论基础。Objective To screen natural small molecule inhibitors of interleukin-6 receptor(IL-6 R)and to predict the mechanism of traditional Chinese medicine(TCM)containing the most IL-6 R inhibitors in the intervention of Coronavirus Disease 2019(COVID-19).Methods The IL-6 R active components were screened by the ADME-Lipinski rule.Taking IL-6 R as the target,the natural small molecule inhibitors of IL-6 R were docked with high-throughput molecules by the Autodock Vina software and Python script,and the natural small molecule compounds with potential IL-6 R inhibitory activity and the core TCM containing these components were obtained.The component-target-pathway network was constructed to predict the mechanism of core TCM in the intervention of COVID-19.Results A total of 1511 components with oral bioavailability(OB)≥30%and drug-likeness(DL)≥0.18 were obtained,involving 372 kinds of TCM.Among them,sesamin had the best docking with IL-6 R,luteolin had the widest source,and Glycyrrhizae Radix et Rhizoma contained the most anti-IL-6 R active components.The results of network pharmacology showed that there were 16 potential targets of Glycyrrhizae Radix et Rhizoma against COVID-19,and seven biological pathways closely related to the occurrence and development of COVID-19 were enriched,including hypoxia-inducible factor-1(HIF-1),vascular endothelial growth factor(VEGF),platelet activation,tumor necrosis factor(TNF),phosphatidylinositol 3-kinase threonine-protein kinase(PI3 K-Akt),interleukin-17(IL-17),Toll like receptor(TLR)and other pathways,which were mainly involved in immune regulation,inflammatory intervention,oxidative stress,anticoagulation and coagulation system regulation.Conclusion Sesamin,luteolin and Glycyrrhizae Radix et Rhizoma have potential intervention ability in multiple ways on the occurrence and development of COVID-19,which can provide a theoretical basis for the development of new drugs against COVID-19.

关 键 词：分子对接技术 白细胞介素6受体 新型冠状病毒肺炎 作用机制 天然小分子抑制剂 芝麻素 木犀草素 甘草 网络药理学 

分 类 号：R932[医药卫生—生药学] R285.5[医药卫生—药学]