基于分子对接技术筛选金银花抗新型冠状病毒活性成分研究.docx

? ? 基于分子对接技术筛选金银花抗新型冠状病毒活性成分研究 ? ? 孙玉 郭中原 陈两绵 关亮俊 房蕴歌 高慧敏 王智民 摘要 目的：运用分子对接技术筛选金银花抗新型冠状病毒（SARS-CoV-2）潜在活性成分，为发现抗SARS-CoV-2先导化合物以及揭示金银花抗新型冠状病毒肺炎（COVID-19）的物质基础提供参考。方法：在文献总结并结合中药系统药理学数据库与分析平台（TCMSP）数据库检索的基础上，建立涵蓋金银花中382个化合物的化学成分库，以SARS-CoV-2 3CL水解酶（3CL Protease，Mpro）以及SARS-CoV-2与血管紧张素转换酶2（ACE2）复合物为分子对接靶标，利用Discovery Studio软件进行分子对接，以打分值大小筛选抗SARS-CoV-2潜在活性成分。结果：金银花中三萜皂苷类成分与SARS-CoV-2 Mpro有较强的结合力，以SARS-CoV-2 Mpro晶体结构复合的原抑制剂N3为阳性对照，7个化合物为其潜在抑制剂;环烯醚萜类和神经酰胺类成分对SARS-CoV-S/ACE2复合物的阻断较好，保留打分值前3%的化合物，10个化合物可作为SARS-CoV-S/ACE2复合物的潜在阻断剂。结论：从金银花中发现16个潜在抗SARS-CoV-2活性成分。本研究为阐明金银花抗击COVID-19的药效物质基础提供参考，同时为发现新的抗SARS-CoV-2先导化合物指明方向。 关键词 金银花;新型冠状病毒肺炎;分子对接;新型冠状病毒Mpro;SARS-CoV-S/ACE2复合物;三萜皂苷;环烯醚萜;神经酰胺 Screening of the Active Components from Flos Lonicerae against SARS-CoV-2 by Molecular Docking SUN Yu1，2，GUO Zhongyuan2，CHEN Liangmian2，GUAN Liangjun2，FANG Yunge1，2，GAO Huimin2，WANG Zhimin2，3 （1 Tianjin University of Traditional Chinese Medicine，Tianjin 300193，China; 2 National Engineering Laboratory for Quality Control Technology of Chinese Materia Medica， Institute of Chinese Materia Medica，China Academy of Chinese Medical Sciences，Beijing 100700，China; 3 School of Pharmacy，Henan University of Chinese Medicine，Zhengzhou 450008，China） Abstract Objective：To screening potential active constituents against SARS-CoV-2 from Lonicera japonica Flos（LJF） by molecular docking technology and provide reference for discovery of lead compounds against SARS-CoV-2 and interpretation of its active substances for the treatment of COVID-19.Methods：The database of 382 chemical constituents from LJF was established based on the literature summary，combining TCMSP database retrieval.SARS-CoV-2 Mpro and SARS-CoV-2/angiotensin-converting enzyme 2（ACE2） were employed as molecular docking targets.Discovery Studio software was used for virtual calculation and the potential active components against SARS-CoV-2 were picked out on the basis of the ranking of docking score.Results：Triterpenoid saponins in LJF had strong