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
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国家重点研发计划“中医药现代化研究”重点专项(2017YFC1701900);中医药行业科研专项(201507002);中国中医科学院自主选题项目(ZZ0808016,ZZ11-095)


Screening of the Active Components from Flos Lonicerae against SARS-CoV-2 by Molecular Docking
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    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,建立涵盖金银花中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。

    Abstract:

    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 affinity with SARS-CoV-2 Mpro and 7 compounds were potential inhibitors,taking SARS-CoV-2 Mpro crystal structure complex inhibitor N3 as the positive control.Iridoids and ceramides had a good blocking effect on SARS-CoV-S/ACE2 complex and 10 compounds were potential blockers.Conclusion:A total of 16 Potential active compounds against SARS-CoV-2 were found from LJF.The present study provides reference for clarifying effective substances of LJF against COVID-19,and discovering lead compounds against SARS-CoV-2 from LJF.

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孙玉,郭中原,陈两绵,关亮俊,房蕴歌,高慧敏,王智民.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[J].世界中医药,2021,(17).

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  • 收稿日期:2021-01-26
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  • 在线发布日期: 2021-09-24
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