Efficient ligand discovery from natural herbs by integrating virtual screening, affinity mass spectrometry and targeted metabolomics
Wang, Zhihua1,2; Liang, Hao3; Cao, Haijie1,2,4; Zhang, Bingjie4; Li, Jun5; Wang, Wenqiong5; Qin, Shanshan4; Wang, Yuefei6; Xuan, Lijiang5; Lai, Luhua3,7,8; Shui, Wenqing4
2019-05-07
Source PublicationANALYST
ISSN0003-2654
Volume144Issue:9Pages:2881-2890
Status已发表
DOI10.1039/c8an02482k
AbstractAlthough 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.
Indexed BySCI
Language英语
Funding ProjectState Key Laboratory of Drug Research[SIMM1601ZZ-03]
WOS Research AreaChemistry
WOS SubjectChemistry, Analytical
WOS IDWOS:000466320100035
PublisherROYAL SOC CHEMISTRY
WOS KeywordTRADITIONAL CHINESE MEDICINE ; EBOLA-VIRUS NUCLEOPROTEIN ; INHIBITORS ; ULTRAFILTRATION ; STRATEGY ; INSIGHT ; NETWORK
Original Document TypeArticle
Citation statistics
Cited Times:3[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://kms.shanghaitech.edu.cn/handle/2MSLDSTB/40831
CollectioniHuman研究所_PI研究组_水雯箐组
Corresponding AuthorXuan, Lijiang; Lai, Luhua; Shui, Wenqing
Affiliation1.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.Chinese Acad Sci, Shanghai Inst Materia Med, State Key Lab Drug Res, 501 Haike Rd,Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China
6.Tianjin Univ Tradit Chinese Med, Tianjin State Key Lab Modern Chinese Med, Tianjin 300193, 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
Corresponding Author AffilicationiHuman Institute
Recommended Citation
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.
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