摘要
目的采用网络药理学与分子对接法探索热毒宁注射液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2020-04-18-2020-04-20借助中药系统药理学数据库和分析平台(TCMSP)及中医药百科全书(ETCM)数据库检索热毒宁注射液组成青蒿、金银花和栀子的化学成分和作用靶点,通过Swiss Target Prediction数据库剔除可能性为0靶点。在GeneCards库及在线人类孟德尔遗传(OMIM)数据库中以"干咳""发热""冠状病毒""肺炎"对应词检索COVID-19相关靶点。Uniprot数据库校正靶点名称,取热毒宁注射液与COVID-19的交集靶点,运用Cytoscape制作热毒宁注射液中药-成分-交集靶点网络,使用DAVID数据库进行GO功能富集和KEGG通路富集预测中药单体化合物治疗COVID-19的作用机制。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6个化合物与血管紧张素转化酶2(ACE2)进行对接。结果热毒宁注射液的中药-成分-交集靶点网络包含3种中药、38个化合物和217个相应靶点,关键靶点涉及PTGS2、NCOA2、DPP4、AR和PTGS1等。GO功能富集分析得到条目P<0.05的341个,KEGG通路富集分析筛选得到135条信号通路。分子对接结果显示,牡荆素、苏丹Ⅲ、6,8-二-c-葡萄糖苷、茵陈黄酮、圣草酚和异鼠李素等6个核心化合物与SARS-CoV-23CL水解酶的结合能分别为-30.98、-30.98、-30.57、-29.31、-29.31和-29.31kJ/mol,与ACE2的结合能分别为-22.19、-21.35、-22.19、-20.52、-22.19和-21.77kJ/mol,均与推荐化学药相似。结论热毒宁注射液中的化合物能通过与SARS-CoV-23CL水解酶和ACE2结合作用于PTGS2、NCOA2、DPP4、AR和PTGS1等靶点调节Toll样受体信号通路、非洲淋巴细胞瘤病毒感染、甲型流感和朊病毒病等通路发挥治疗COVID-19作用。
Objective Network pharmacology and molecular docking were employed to explore the potential mechanism and active components of Reduning Injection for the treatment of coronavirus 2019(COVID-19).Methods From April 18 to20,2020,the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the Encyclopedia of Traditional Chinese Medicine(ETCM)databases were used to search the chemical constituents and action targets of Reduning Injection,which were composed of artemisia annua,honeysuckle and gardenia jasminoides,and the possible targets were eliminated by Swiss Target Prediction database.The corresponding words of"dry cough""fever""coronavirus"and"pneumonia"were searched in GeneCards database and the Online Mendelian Inheritance in Man(OMIM)database.Uniprot database corrected the COVID-19 target and the target of heat treatment and injection.The Cytoscape software was used to produce the traditional Chinese medicine target network.After that,DAVID database was used to enrich GO function and KEGG pathway to predict the mechanism of action of Chinese medicine monomer compounds in the treatment of COVID-19.All compounds were docking Novel coronavirus(SARS-CoV-2)3 CL hydrolase,and 6 compounds with the lowest binding energy were selected to join the angiotensin-converting enzyme 2(ACE2).Results The compound target network of Reduning Injection included 3 kinds of traditional Chinese medicine,38 compounds and 217 corresponding targets.The key targets involved PTGS2,NCOA2,DPP4,AR,PTGS1,etc.341 items with P<0.05 were obtained by GO functional enrichment analysis,and 135 signal pathways were screened by KEGG pathway enrichment analysis.The results of molecular docking showed that the binding energies of the six core compounds:vitexin_qt,SudanⅢ,6,8-di-c-glucosylapigenin_qt,Areapillin,Eriodyctiol(flavanone),Isorhamnetin with SARS-CoV-23 CL hydrolase were-30.98,-30.98,-30.57,-29.31,-29.31 and-29.31 kJ/mol,respectively,and the binding energies with ACE2 were-22.19,-21.35,-22.19,-20.52,-22.19 an
作者
汪晶
曹灿
史银玥
楚玉玺
崔瑛
冯静
李玲玲
巫晓慧
WANG Jing;CAO Can;SHI Yin-yue;CHU Yu-xi;CUI Ying;FENG Jing;LI Ling-ling;WU Xiao-hui(Department of Pharmacy,the Third Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450000,China;School of Medicine,Henan University of Traditional Chinese Medicine,Zhengzhou 450046,China;Henan University of Traditional Chinese Medicine Respiratory Disease Prevention and Treatment of Traditional Chinese Medicine Province and Ministry of Collaborative Innovation Center,Zhengzhou 450000,China)
出处
《社区医学杂志》
CAS
2021年第16期988-995,共8页
Journal Of Community Medicine
基金
国家自然科学基金(81473368)。
关键词
网络药理学
热毒宁注射液
新型冠状病毒肺炎
作用机制
分子对接
network pharmacology
Reduning Injection
coronavirus disease 2019
mechanism of action
molecular docking
