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基于多靶点分子对接初探宣肺化浊方治疗新型冠状病毒肺炎的物质基础
Material Basis of Xuanfei Huazhuo Prescription in Treatment of COVID-19 by Multi-target Molecular Docking
- 中国实验方剂学杂志 2020年26卷第16期 页码：32-39
- 作者机构：
1.甘肃中医药大学 附属医院，兰州 730000
2.甘肃中医药大学 甘肃省高校重大疾病分子医学与 中医药防治研究重点实验室，敦煌医学与转化省部共建教育部重点实验室，兰州 730000
3.兰州大学 第一医院，兰州 730000
- 作者简介：
冯彩琴，硕士，住院医师，从事中西医结合防治肿瘤研究，E-mail：1434189112@qq.com
靳晓杰，副教授，硕士生导师，从事计算机辅助药物设计与中药现代化研究，E-mail：jinlovedream@163.com
刘永琦，教授，博士生导师，从事中医药免疫与干细胞生物学研究，E-mail：liuyongqi73@163.com
- 基金信息：甘肃省高校重大疾病分子医学与中医药防治研究重点实验室新型冠状病毒防治科研专项开放基金项目(FZYX20-3)
DOI：10.13422/j.cnki.syfjx.20201702
中图分类号： R2-0;R22;R285.5;R289-
网络出版日期：2020-06-11，
纸质出版日期：2020-08-20
- 稿件说明：
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冯彩琴,张志明,张月梅等.基于多靶点分子对接初探宣肺化浊方治疗新型冠状病毒肺炎的物质基础[J].中国实验方剂学杂志,2020,26(16):32-39.
FENG Cai-qin,ZHANG Zhi-ming,ZHANG Yue-mei,et al.Material Basis of Xuanfei Huazhuo Prescription in Treatment of COVID-19 by Multi-target Molecular Docking[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(16):32-39.
冯彩琴,张志明,张月梅等.基于多靶点分子对接初探宣肺化浊方治疗新型冠状病毒肺炎的物质基础[J].中国实验方剂学杂志,2020,26(16):32-39. DOI： 10.13422/j.cnki.syfjx.20201702.
FENG Cai-qin,ZHANG Zhi-ming,ZHANG Yue-mei,et al.Material Basis of Xuanfei Huazhuo Prescription in Treatment of COVID-19 by Multi-target Molecular Docking[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(16):32-39. DOI： 10.13422/j.cnki.syfjx.20201702.
摘要
目的
2
运用分子对接、靶点反向预测及反向分子对接技术探索宣肺化浊方治疗新型冠状病毒肺炎（COVID-19）的物质基础及可能的分子机制。
方法
2
在中药系统药理学分析平台（TCMSP）检索宣肺化浊方中10味中药化合物，以血管紧张素转换酶2（ACE2），白细胞介素-6受体（IL-6R）为靶蛋白，运用分子对接筛选方中与ACE2，IL-6R对接打分较好且符合类药性的化合物，并进行化学信息学层次聚类分析；利用 Swiss Target Prediction 预测化合物潜在靶点；运用Cytoscape 构建化合物-靶点网络；利用STRING 分析靶点蛋白互相作用。
结果
2
宣肺化浊方中针对ACE2潜在有活性的化合物共312个，活性较强的化合物15个；针对IL-6R符合条件的活性化合物共100个，活性较强的化合物3个，对活性较强的化合物进行化学信息学层次聚类分析发现大多属于黄酮类。药味-有效成分-靶点网络包含药材10味、化合物126个、靶点130个；STRING分析显示磷脂酰肌醇3激酶调节亚基1（PIK3R1），肉瘤基因（SRC），丝苏氨酸蛋白激酶1（AKT1），雄激素受体（AR）和表皮生长因子受体（EGFR）等蛋白可能是宣肺化浊方起效的关键靶点。
结论
2
本研究基于多靶点分子对接虚拟筛选初步得到宣肺化浊方抗病毒、抗炎的物质基础，同时结合靶点反向预测和分析探索该方治疗COVID-19潜在作用靶点和分子机制，为宣肺化浊方及其相关方药的多角度挖掘和单体成分的现代化开发提供线索。
Abstract
Objective
2
Structure-based angiotension converting enzyme 2 (ACE2) and interleukin-6R (IL-6R) were taken as the target proteins to in the investigation of the material basis of Xuanfei Huazhuo prescription in the treatment of coronavirus disease-2019 (COVID-19) by molecular docking.
Method
2
The compounds in Xuanfei Huazhuo prescription were retrieved through TCMSP. Structure-based ACE2 and IL-6R were taken as the target proteins to screen out the compounds with a better activity by molecular docking
and analyze structural properties of these compounds. Furthermore
the potential molecular mechanism of Xuanfei Huazhuo prescription in the treatment of COVID-19 was analyzed by target reverse prediction.
Result
2
There were 312 potentially active compounds in Xuanfei Huazhuo prescription
including 75 highly active compounds and 15 highly active compounds for ACE2. There were 100 eligible active compounds and 3 highly active compounds for IL-6R
most of which belong to flavonoids. The herb-component-target network included 10 herbs
126 compounds and 130 targets. String analysis showed that PIK3R1
SRC
AKT1
AR and EGFR might be the key targets of Xuanfei Huazhuo prescription.
Conclusion
2
Based on the virtual screening of multi-target molecular docking
the anti-virus and anti-inflammatory material basis of Xuanfei Huazhuo prescription was preliminarily obtained. At the same time
based on the reverse prediction and analysis
potential targets and molecular mechanism of the recipe in the treatment of COVID-19 were explored
so as to provide clues for the multi-angle mining of Xuanfei Huazhuo prescription and its relevant prescriptions and the modernization development of monomer components.
关键词
Keywords
references
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