Material Basis of Xuanfei Huazhuo Prescription in Treatment of COVID-19 by Multi-target Molecular Docking

FENG Cai-qin; ZHANG Zhi-ming; ZHANG Yue-mei; WANG Yan-ru; YONG Wen-xing; TAI An-ning; LI Dan-gui; JIN Xiao-jie; LIU Yong-qi

doi:10.13422/j.cnki.syfjx.20201702

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Material Basis of Xuanfei Huazhuo Prescription in Treatment of COVID-19 by Multi-target Molecular Docking

更新时间：2023-07-12

- Material Basis of Xuanfei Huazhuo Prescription in Treatment of COVID-19 by Multi-target Molecular Docking
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 16, Pages: 32-39(2020)
- 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：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20201702
  CLC： R2-0;R22;R285.5;R289
- Published Online：11 June 2020，
  
  Published：20 August 2020
- 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

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

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

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

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

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

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

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

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

XU X , CHEN P , WANG J , et al . Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission [J]. Sci China Life Sci , 2020 , 63 ( 3 ): 457 - 460 .

XU Z , SHI L , WANG Y , et al . Pathological findings of COVID-19 associated with acute respiratory distress syndrome [J]. Lancet Respir Med , 2020 , 8 ( 4 ): 420 - 422 .

HUANG C L , WANG Y M , LI X W , et al . Clinical features of patients infected with 2019 novel coronavirus in Wuhan,China [J]. Lancet , 2020 , 395 ( 10223 ): 497 - 506 .

刘东玲 , 王浩嘉 , 任伟钰 , 等 . 宣肺化浊方治疗新型冠状病毒感染肺炎的网络药理学分析 [J]. 中国实验方剂学杂志 , 2020 , 26 ( 16 ): 40 - 49 .

王鑫 , 张志明 , 王功臣 , 等 . “甘肃方剂”在新型冠状病毒肺炎防治中的应用策略分析 [J]. 中国实验方剂学杂志 , 2020 , 26 ( 16 ): 21 - 25 .

张煜卓 , 戚涵姝 , 谷笑雨 , 等 . 分子对接在药物虚拟筛选中的应用进展 [J]. 广州化学 , 2017 , 42 ( 6 ): 62 - 67 .

王文军 , 丁一 , 窦芳 , 等 . 分子对接在中药药效物质筛选及作用机制研究中的应用进展 [J]. 中国药师 , 2018 , 21 ( 6 ): 1020 - 1023 .

李研 , 骆亚莉 , 刘永琦 , 等 . 基于分子对接探讨红芪中小分子拮抗肿瘤坏死因子受体1的可能性 [J]. 中国实验方剂学杂志 , 2019 , 25 ( 17 ): 173 - 180 .

吴昊 , 王佳琪 , 杨雨薇 , 等 . 基于网络药理学和分子对接技术初步探索“清肺排毒汤”抗新型冠状病毒肺炎作用机制 [J]. 药学学报 , 2020 , 55 ( 3 ): 374 - 383 .

XING W , BUSINO L , HINDS T R , et al . SCF FBXL3 ubiquitin ligase targets cryptochromes at their cofactor pocket [J]. Nature , 2013 , 496 ( 7443 ): 64 - 68 .

DUAN Y , CHEN L , CHEN Y , et al . c-Src binds to the cancer drug Ruxolitinib with an active conformation [J]. PLoS One , 2014 , 9 ( 9 ): e106225 .

LIN K , LIN J , WU W I , et al . An ATP-site on-off switch that restricts phosphatase accessibility of Akt [J]. Sci Signal , 2012 , 5 ( 223 ): ra37-ra37 .

SATOSHI S , YOUICHI K , SHIGERU I , et al . Structure-based approach for the discovery of pyrrolo[3,2-d]pyrimidine-based EGFR T790M/L858R mutant inhibitors [J]. ACS Med Chem Lett , 2013 , 4 ( 2 ): 201 - 205 .

YANG C L , LIN Y S , LIU K F , et al . Hepatoprotective mechanisms of Taxifolin on carbon tetrachloride-induced acute liver injury in mice [J]. Nutrients , 2019 , 11 ( 11 ): 2655 .

HU C , YE J W , ZHAO L C , et al . 5,7,3',4'-Flavan-on-ol (taxifolin) protects against acetaminophen-induced liver injury by regulating the glutathione pathway [J]. Life Sci , 2019 , 236 : 116939 .

LIU F , MA Y , XU Y . Taxifolin shows anticataractogenesis and attenuates diabetic retinopathy in STZ-diabetic rats via suppression of aldose reductase,oxidative stress and MAPK signaling pathway [J]. Endocr Metab Immune Disord Drug Targets , 2020 , 20 ( 4 ): 599 - 608 .

LI J , HU L , ZHOU T , et al . Taxifolin inhibits breast cancer cells proliferation,migration and invasion by promoting mesenchymal to epithelial transition via β -catenin signaling [J]. Life Sci , 2019 , 232 : 116617 .

KOOSHA S , MOHAMED Z , SINNIAH A , et al . Evaluation of anti-tumorigenic effects of diosmetin against human colon cancer xenografts in athymic nude mice [J]. Molecules , 2019 , 24 ( 14 ): 2522 .

OAK C , KHALIFA A O , ISALI I , et al . Diosmetin suppresses human prostate cancer cell proliferation through the induction of apoptosis and cell cycle arrest [J]. Int J Oncol , 2018 , 53 ( 2 ): 835 - 843 .

EID H M , HADDAD P S . The antidiabetic potential of quercetin:underlying mechanisms [J]. Current Medicinal Chemistry , 2017 , 24 ( 4 ): 355 - 364 .

SINGH A K , PATEL P K , CHOUDHARY K , et al . Uercetin and coumarin inhibit dipeptidyl peptidase-Ⅳ and exhibits antioxidant properties: in silico,in vitro,ex vivo [J]. Biomolecules , 2020 , 10 ( 2 ): E207 .

WANG X , DENG R , DONG J , et al . Eriodictyol ameliorates lipopolysaccharide-induced acute lung injury by suppressing the inflammatory COX-2/NLRP3/NF- κ B pathway in mice [J]. J Biochem Mol Toxicol , 2020 , 34 ( 3 ): e22434 .

XIE Y , JI R , HAN M . Eriodictyol protects H9c2 cardiomyocytes against the injury induced by hypoxia/reoxygenation by improving the dysfunction of mitochondria [J]. Exp Ther Med , 2019 , 17 ( 1 ): 551 - 557 .

龚莉虹，余琳媛，胡乃华，等 . 连翘抗炎药效物质基础及其作用机理研究进展 [J]. 中药与临床 , 2019 , 10 ( 1 ): 47 - 53 .

贾军 , 费乔曼 , 邱曼曼 , 等 . 芫花素对于MC3T3-E1细胞向成骨细胞分化的影响 [J]. 现代药物与临床 , 2020 , 35 ( 1 ): 12 - 15 .

刘文武 , 蒋晓文 , 张帅 , 等 . 羌活中香豆素类化学成分及其抗氧化活性研究 [J]. 中草药 , 2019 , 50 ( 6 ): 1310 - 1315 .

DONG X , ZENG Y , LIU Y , et al . Aloe-emodin:a review of its pharmacology,toxicity,and pharmacokinetics [J]. Phytother Res , 2020 , 34 ( 2 ): 270 - 281 .

AKEV N , CANDOKEN E , ERDEM K S . Comparative study on the anticancer drug potential of a lectin purified from aloe vera and aloe-emodin [J]. Asian Pac J Cancer Prev , 2020 , 21 ( 1 ): 99 - 106 .

李冰涛 , 翟兴英 , 李佳 , 等 . 基于网络药理学葛根解热作用机制研究 [J]. 药学学报 , 2019 , 54 ( 8 ): 1409 - 1416 .

史桐凡 , 周谷城 , 张利英 , 等 . 宣肺化浊加减方治疗新型冠状病毒肺炎40例临床疗效观察 [J]. 中国实验方剂学杂志 , 2020 , 26 ( 16 ): 26 - 31 .

ZAKARYAN H , ARABYAN E , OO A , et al . Flavonoids:promising natural compounds against viral infections [J]. Arch Virol , 2017 , 162 ( 9 ): 2539 - 2551 .

CHO W K , WEERATUNGA P , LEE B H , et al . Epimedium koreanum nakai displays broad spectrum of antiviral activity in vitro and in vivo by inducing cellular antiviral state [J]. Viruses , 2015 , 7 ( 1 ): 352 - 377 .

SCHWARZ S , SAUTER D , WANG K , et al . Kaempferol derivatives as antiviral drugs against the 3a channel protein of coronavirus [J]. Planta Medica , 2014 , 80 ( 2/3 ): 177 - 182 .

PENG L Y , YUAN M , SHI H T , et al . Protective effect of piceatannol against acute lung injury through protecting the integrity of air-blood barrier and modulating the TLR4/NF- κ B signaling pathway activation [J]. Front Pharmacol , 2020 , 10 : 1613 .

COSTA F P D , PUTY B , NOGUEIRA L S , et al . Piceatannol increases antioxidant defense and reduces cell death in human periodontal ligament fibroblast under oxidative stress [J]. Antioxidants (Basel) , 2019 , 9 ( 1 ): 16 .

ZHOU L , YANG F , LI G , et al . Coptisine induces apoptosis in human hepatoma cells through activating 67-kDa laminin receptor/cGMP signaling [J]. Front Pharmacol , 2018 , 9 : 517 .

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