基于网络药理学和高通量分子对接虚拟筛选参麦注射液治疗新型冠状病毒肺炎活性成分及作用机制

Virtual screening the active ingredient and mechanism of Shenmai injection in treatment of novel coronavirus pneumonia based on network pharmacology and high throughput molecular docking

目的筛选参麦注射液治疗新型冠状病毒肺炎(COVID-19)的活性成分并探讨其作用机制。方法基于网络药理学和高通量分子对接技术,从TCMSP、中药分子作用机制的网络药理学在线分析工具(BATMAN-TCM)及Targetnet数据库中检索参麦注射液的化合物和预测靶点,并构建成分-靶点网络;从在线人类孟德尔遗传数据库(OMIM)和GeneCards数据库中检索"coronavirus pneumonia"相关基因,与化合物作用靶点共有的部分构建靶基因间的蛋白相互作用网络;使用DAVID6.8进行基因功能、通路富集分析;通过PDB数据库获取蛋白质的晶体结构,采用AutoDock Vina和Python脚本进行高通量分子对接。结果共获得27个化合物和224个靶基因,鉴定出干预冠状病毒的15个核心成分与15个核心靶点,分别为CASP3、NOS2、PARP1、CASP8、NOS3、BCL2、ADA、OPRM1、TGFB1、TLR9、ACHE、SLC29A1、BAX、ADK、PNP。核心靶点主要作用于肺结核、癌症通路、乙型肝炎、细胞凋亡等信号通路。虚拟筛选后得到与冠状病毒相关靶点对接较好的成分有薯蓣皂苷元、豆甾醇、β-谷甾醇、人参皂苷Rh1苷元。结论本研究筛选出了参麦注射液干预冠状病毒的主要活性成分及作用靶点,为参麦注射液治疗COVID-19提供参考。

Objective To virtual screen the active ingredient of Shenmai injection in treatment of Novel Coronavirus Pneumonia and discuss the potential mechanism based on network pharmacology and high throughput molecular docking.Methods Based on network pharmacology and high-throughput molecular docking technology,the compounds and predicted targets of Shenmai injection were retrieved from TCMSP,BATMAN-TCM and Targetnet databases,and the composition target map was constructed.The genes related to coronavirus pneumonia were retrieved from OMIM and GeneCards databases,and the PPI network between target genes was constructed by searching the common parts of target genes;David 6.8 was used to analyze gene function and pathway enrichment,and PDB database was used to obtain protein crystal structure,and Autodock Vina and python scripts were used for high-throughput molecular docking.Results A total of 27 compounds and 224 target genes were obtained.15 core components and 15 core targets for the treatment of coronavirus pneumonia were identified:CASP3,NOS2,PARP1,CASP8,NOS3,BCL2,ADA,OPRM1,TGFB1,TLR9,ACHE,SLC29A1,BAX,ADK,and PNP.The enrichment analysis showed that the core targets acted on the signaling pathways such as Tuberculosis,Pathways in cancer,Hepatitis B and Apoptosis.The better components of Novel Coronavirus Pneumonia related targets were diosgenin,stigmasterol,beta-sitosterol and ginsenoside Rh1_qt obtained by virtual screening.Conclusion This study screened out the active ingredient and tarket of Shenmai Injection in treatment of Novel Coronavirus Pneumonia.It laid a foundation for the further clinical application of Shenmai injection and development of novel coronavirus pneumonia drugs.