基于网络药理学与分子对接方法的疏风解毒胶囊治疗新型冠状病毒肺炎(COVID-19)的作用机制与活性成分研究

Investigation on mechanism and active components of Shufeng Jiedu Capsule in treatment of COVID-19 based on network pharmacology and molecular docking

目的采用网络药理学与分子对接法探索疏风解毒胶囊治疗新型冠状病毒肺炎(COVID-19)的潜在作用机制与活性成分。方法借助TCMSP数据库检索疏风解毒胶囊组成药材板蓝根、虎杖、连翘、芦根、败酱草、马鞭草、柴胡、甘草的化学成分和作用靶点,通过SwissTargetPrediction数据库剔除可能性为0的靶点。以"冠状病毒(coronavirus)""肺炎(pneumonia)""咳嗽(cough)""发热(fever)"为检索词在GeneCards及OMIM数据库中检索疾病相应靶点。通过Uniprot数据库校正靶点名称,取疏风解毒胶囊与疾病靶点交集,进而运用Cytoscape 3.7.2软件构建中药-化合物-靶点网络进行可视化,通过DAVID数据库进行GO功能富集分析和KEGG通路富集分析,预测交集靶点作用机制,并绘制柱状图及气泡图进行可视化。然后将所有化合物与新型冠状病毒(SARS-CoV-2)3CL水解酶进行对接,选取结合能最小的前5个化合物与血管紧张素转化酶II(ACE2)进行对接。结果中药-化合物-靶点网络包含了8种中药,157个化合物和相应靶点260个,关键靶点涉及PTGS2、ESR1、AR等。GO功能富集分析得到条目393个(P<0.05),KEGG通路富集分析筛选得到139条信号通路。分子对接结果显示6-(3-氧吲哚-2-亚立德)吲哚[2,1-b]喹唑啉-12-酮、荷包牡丹碱、大黄素甲醚葡萄糖苷、双氢轮叶十齿草碱和甘草异黄烷酮5个核心化合物与SARS-CoV-23CL水解酶及ACE2的结合能较推荐化学药小。结论疏风解毒胶囊中的化合物能通过与SARS-CoV-23CL水解酶及ACE2结合作用于PTGS2、ESR1、AR等靶点调节人巨细胞病毒感染、卡波西肉瘤相关疱疹病毒感染、IL-17信号通路等信号通路、小细胞肺癌等发挥治疗COVID-19作用。

Objective To explore the novel coronavirus disease 2019(COVID-19)treatment mechanism and active ingredients of Shufeng Jiedu Capsule by network pharmacology and molecular docking.Methods TCMSP databases were used to search the chemical composition and target of Shufeng Jiedu Capsule,which was composed of Isatidis Radix,Polygonum cuspidatum,Forsythia suspensa,Phragmitis Rhizoma,Patrinia,Verbena officinalis,Bupleurum chinense,and Glycyrrhiza uralensis.The Swiss target prediction database was used to remove the target with possibility of 0.The corresponding targets of the disease were searched in the GeneCards and OMIM databases with the key words of"coronavirus","pneumonia","cough",and"fever".Through the UniProt databases to correct the name of the target point,take the intersection of Shufeng Jiedu Capsule and the disease target point,then use the software of Cytoscape 3.7.2 to build the network of traditional Chinese medicine-compound-target for visualization,through DAVID databases to carry out the GO function enrichment analysis and KEGG pathway enrichment analysis,predict the interaction mechanism of the target,and draw the column and bubble chart for visualization.The novel coronavirus(SARS-CoV-2)3 CL hydrolase was then docking with all compounds and the first five compounds with the least binding energy were selected for docking with angiotensin-converting enzyme II(ACE2).Results The traditional Chinese medicine-compound-target compound target network contains eight kinds of traditional Chinese medicine-compound-target,157 compounds and 260 corresponding targets.The key targets were PTGS2,ESR1,AR,etc.There were 393 items in GO functional enrichment analysis(P<0.05),and 139 signaling pathways in KEGG pathway enrichment analysis.Molecular docking results showed that SARS-CoV-23 CL hydrolase and ACE2 binding energy of the five core compounds,including 6-(3-oxoindolin-2-ylidene)indolo[2,1-b]quinazolin-12-one,bicuculline,physciondiglucoside,dihydroverticillatine,and licoisoflavanone,was smaller than that of recommended chemical drugs,and the binding energy to ACE2 was similar to that of the recommended chemical drug.Conclusion The compounds in Shufeng Jiedu Capsule can regulate the signaling pathway of human cytomegalovirus infection,Kaposi’s sarcoma associated herpesvirus infection,IL-17 signaling pathway,small cell lung cancer,etc.to treat COVID-19 by binding with SARS-CoV-23 CL hydrolase and ACE2.