南方医科大学学报

南方医科大学学报 ›› 2020, Vol. 40 ›› Issue (05): 616-623.doi: 10.12122/j.issn.1673-4254.2020.05.02

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基于网络药理学和分子对接技术分析清肺排毒汤治疗COVID-19的机制

鄢海燕，邹 妍，邹纯才   

  • 出版日期:2020-05-20 发布日期:2020-05-20
  • 基金资助:

Mechanism of Qingfei Paidu decoction for treatment of COVID-19: analysis based on network pharmacology and molecular docking technology

  

  • Online:2020-05-20 Published:2020-05-20

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摘要： 目的 基于网络药理学和分子对接技术分析清肺排毒汤治疗COVID-19的作用靶点、信号通路和生物学功能。方法 利用TCMSP、SwissTarget Prediction、CooLGeN、GeneCards、DAVID等数据库，分析清肺排毒汤中麻黄、半夏等21味药所含的活性成分及其靶点蛋白，筛选与COVID-19疾病共有的靶点蛋白及其信号通路与生物学功能，采用Gephi软件构建清肺排毒汤药味-活性成分-作用靶点-生物学功能网络图。结果 清肺排毒汤中麻黄、半夏、甘草、冬花、紫菀、枳实等18味药的MOL000519、MOL000554、MOL004798、MOL004824、MOL010428、MOL013443等163个活性成分通过调控ACE、ACE2、AGTR1、FURIN、TNF、CASP3、CASP6、DPP4、MCL1、POLD1等10个蛋白靶点激活肾素-血管紧张素系统信号通路和细胞凋亡信号通路，发挥肾素-血管紧张素对血容量的调节、肾素-血管紧张素对全身动脉血压的调节等42种生物学功能治疗COVID-19。初步分子对接结果显示，核心活性成分MOL000519（来自半夏）、MOL000554（来自冬花）、MOL004798（来自麻黄）、MOL004824（来自甘草）、MOL010428（来自紫菀）、MOL013443（来自枳实）等与SARS-CoV-2 3CL水解酶有较好的亲合力，可形成稳定构象，具有较好结合活性（结合能≤-5 kJ/mol）。结论 清肺排毒汤以多药味、多靶点、多信号通道和多生物学功能发挥治疗COVID-19作用，该研 究可为深入阐释清肺排毒汤治疗COVID-19的药理作用及机制提供参考。

Abstract: Objective To explore the target, signaling pathways and their biological functions of Qingfei Paidu Decoction in the treatment of COVID-19 based on network pharmacology and molecular docking technology. Methods The active components and target proteins in 21 drugs such as Ephedrae Herba and Pinelliae Rhizoma in Qingfei Paidu decoction were analyzed, and the signaling pathways and biological functions of the target proteins common with COVID-19 were screened by using TCMSP, Swiss Target Prediction, CooLGeN, GeneCards, DAVID and other databases. The network diagram of Qingfei Paidu decoction was constructed using Gephi software. Results We identified 163 active ingredients, including MOL004798, MOL000519, MOL004824, MOL000554, MOL010428, and MOL013443, from 18 drugs in Qingfei Paidu decoction (such as Ephedrae Herba, Pinelliae Rhizoma, Glycyrrhizae Radix Et Rhiizoma, Farfarae Flos, Asteris Radix Et Rhizoma and Aurantii Fructus Immaturus). These ingredients activate renin-angiotensin system signaling pathway and apoptosis signaling pathway by regulating 10 protein targets (ACE, ACE2, AGTR1, FURIN, TNF, CASP3, CASP6, DPP4, MCL1 and POLD1) to execute 42 biological functions such as renin-angiotensin regulation of blood volume and systemic arterial blood pressure to treat COVID-19. The results of preliminary molecular docking showed that MOL000519 (from Pinelliae Rhizoma), MOL000554 (from Farfarae Flos), MOL004798 (from Ephedrae Herba), MOL004824 (from Glycyrrhizae Radix Et Rhiizoma), MOL010428 (from Asteris Radix Et Rhizoma), and MOL013443 (from Aurantii Fructus Immaturus) had good affinity with SARS-CoV-2 3CL hydrolase to form complexes with stable conformations and high binding activity (binding energy ≤- 5 kJ/mol). Conclusion Qingfei Paidu decoction can treat COVID-19 through its multiple medicinal ingredients that have multiple targets and involve multiple signaling pathways for different biological functions. Our finding provides reference for further investigation into the pharmacological mechanism of Qingfei Paidu decoction in treating COVID-19.