Efficient ligand discovery from natural herbs by integrating virtual screening, affinity mass spectrometry and targeted metabolomics

doi:10.1039/c8an02482k

	Efficient ligand discovery from natural herbs by integrating virtual screening, affinity mass spectrometry and targeted metabolomics
	Wang, Zhihua 1,2; Liang, Hao 3; Cao, Haijie 1,2,4; Zhang, Bingjie 4; Li, Jun 6; Wang, Wenqiong 6; Qin, Shanshan 4; Wang, Yuefei 5; Xuan, Lijiang 6; Lai, Luhua 3,7,8
刊名	ANALYST
	2019-05-07
卷号	144 期号:9 页码:2881-2890
ISSN号	0003-2654
DOI	10.1039/c8an02482k
通讯作者	Xuan, Lijiang(ljxuan@simm.ac.cn) ; Lai, Luhua(lhlai@pku.edu.cn) ; Shui, Wenqing(shuiwq@shanghaitech.edu.cn)
英文摘要	Although natural herbs have been a rich source of compounds for drug discovery, identification of bioactive components from natural herbs suffers from low efficiency and prohibitive cost of the conventional bioassay-based screening platforms. Here we develop a new strategy that integrates virtual screening, affinity mass spectrometry (MS) and targeted metabolomics for efficient discovery of herb-derived ligands towards a specific protein target site. Herb-based virtual screening conveniently selects herbs of potential bioactivity whereas affinity MS combined with targeted metabolomics readily screens candidate compounds in a high-throughput manner. This new integrated approach was benchmarked on screening chemical ligands that target the hydrophobic pocket of the nucleoprotein (NP) of Ebola viruses for which no small molecule ligands have been reported. Seven compounds identified by this approach from the crude extracts of three natural herbs were all validated to bind to the NP target in pure ligand binding assays. Among them, three compounds isolated from Piper nigrum (HJ-1, HJ-4 and HJ-6) strongly promoted the formation of large NP oligomers and reduced the protein thermal stability. In addition, cooperative binding between these chemical ligands and an endogenous peptide ligand was observed, and molecular docking was employed to propose a possible mechanism. Taken together, we established a platform integrating in silico and experimental screening approaches for efficient discovery of herbderived bioactive ligands especially towards non-enzyme protein targets.
资助项目	Shanghai Tech University ; National Key Research and Development Program of China[2018YFA0507004] ; National Key Research and Development Program of China[2016YFA0502303] ; National Natural Science Foundation of China[21633001] ; National Natural Science Foundation of China[81473111] ; National Natural Science Foundation of China[21702219] ; National Natural Science Foundation of China[81773863] ; State Key Laboratory of Drug Research[SIMM1601ZZ-03]
WOS关键词	TRADITIONAL CHINESE MEDICINE ; EBOLA-VIRUS NUCLEOPROTEIN ; INHIBITORS ; ULTRAFILTRATION ; STRATEGY ; INSIGHT ; NETWORK
WOS研究方向	Chemistry
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000466320100035
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/289919]
专题	中国科学院上海药物研究所
通讯作者	Xuan, Lijiang; Lai, Luhua; Shui, Wenqing
作者单位	1.Nankai Univ, Coll Pharm, Tianjin 300071, Peoples R China 2.Tianjin Joint Acad Biotechnol & Med, High Throughput Mol Drug Discovery Ctr, Tianjin 300457, Peoples R China 3.Peking Univ, Acad Adv Interdisciplinary Studies, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China 4.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China 5.Tianjin Univ Tradit Chinese Med, Tianjin State Key Lab Modern Chinese Med, Tianjin 300193, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Materia Med, State Key Lab Drug Res, 501 Haike Rd,Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China 7.Peking Univ, Acad Adv Interdisciplinary Studies, Ctr Quantitat Biol, Beijing 100871, Peoples R China 8.Peking Univ, Coll Chem & Mol Engn, State Key Lab Struct Chem Unstable & Stable Speci, Beijing Natl Lab Mol Sci, Beijing 100871, Peoples R China
推荐引用方式 GB/T 7714	Wang, Zhihua,Liang, Hao,Cao, Haijie,et al. Efficient ligand discovery from natural herbs by integrating virtual screening, affinity mass spectrometry and targeted metabolomics[J]. ANALYST,2019,144(9):2881-2890.
APA	Wang, Zhihua.,Liang, Hao.,Cao, Haijie.,Zhang, Bingjie.,Li, Jun.,...&Shui, Wenqing.(2019).Efficient ligand discovery from natural herbs by integrating virtual screening, affinity mass spectrometry and targeted metabolomics.ANALYST,144(9),2881-2890.
MLA	Wang, Zhihua,et al."Efficient ligand discovery from natural herbs by integrating virtual screening, affinity mass spectrometry and targeted metabolomics".ANALYST 144.9(2019):2881-2890.