Novel Chemical Ligands to Ebola Virus and Marburg Virus Nucleoproteins Identified by Combining Affinity Mass Spectrometry and Metabolomics Approaches

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	Novel Chemical Ligands to Ebola Virus and Marburg Virus Nucleoproteins Identified by Combining Affinity Mass Spectrometry and Metabolomics Approaches
	Fu, Xu 1,2; Wang, Zhihua 2,3; Li, Lixin 2; Dong, Shishang 2; Li, Zhucui 4; Jiang, Zhenzuo 5; Wang, Yuefei 5; Shui, Wenqing 6
刊名	SCIENTIFIC REPORTS
	2016-07-12
卷号	6
英文摘要	The nucleoprotein (NP) of Ebola virus (EBOV) and Marburg virus (MARV) is an essential component of the viral ribonucleoprotein complex and significantly impacts replication and transcription of the viral RNA genome. Although NP is regarded as a promising antiviral druggable target, no chemical ligands have been reported to interact with EBOV NP or MARV NP. We identified two compounds from a traditional Chinese medicine Gancao (licorice root) that can bind both NPs by combining affinity mass spectrometry and metabolomics approaches. These two ligands, 18 beta-glycyrrhetinic acid and licochalcone A, were verified by defined compound mixture screens and further characterized with individual ligand binding assays. Accompanying biophysical analyses demonstrate that binding of 18 beta-glycyrrhetinic acid to EBOV NP significantly reduces protein thermal stability, induces formation of large NP oligomers, and disrupts the critical association of viral ssRNA with NP complexes whereas the compound showed no such activity on MARV NP. Our study has revealed the substantial potential of new analytical techniques in ligand discovery from natural herb resources. In addition, identification of a chemical ligand that influences the oligomeric state and RNA-binding function of EBOV NP sheds new light on antiviral drug development.
WOS标题词	Science & Technology
类目[WOS]	Multidisciplinary Sciences
研究领域[WOS]	Science & Technology - Other Topics
关键词[WOS]	XANTHINE-OXIDASE ; LC-MS ; ULTRAFILTRATION ; INHIBITORS ; RNA ; GLYCYRRHIZIN ; REPLICATION ; DISEASE ; COMPLEX ; CHROMATOGRAPHY
收录类别	SCI
语种	英语
WOS记录号	WOS:000379389600002
内容类型	期刊论文
源URL	[http://124.16.173.210/handle/834782/2909]
专题	天津工业生物技术研究所_生物质谱与定量生物学研究水雯箐_期刊论文
作者单位	1.Tianjin Univ Sci Technol, Coll Biotechnol, Tianjin 300457, Peoples R China 2.Tianjin Joint Acad Biotechnol & Med, High Throughput Mol Drug Discovery Ctr, Tianjin 300457, Peoples R China 3.Nankai Univ, Coll Pharm, Tianjin 300071, Peoples R China 4.Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Tianjin 300308, Peoples R China 5.Tianjin Univ Tradit Chinese Med, Tianjin State Key Lab Modern Chinese Med, Tianjin 300193, Peoples R China 6.ShanghaiTech Univ, Human Inst, Shanghai 201210, Peoples R China
推荐引用方式 GB/T 7714	Fu, Xu,Wang, Zhihua,Li, Lixin,et al. Novel Chemical Ligands to Ebola Virus and Marburg Virus Nucleoproteins Identified by Combining Affinity Mass Spectrometry and Metabolomics Approaches[J]. SCIENTIFIC REPORTS,2016,6.
APA	Fu, Xu.,Wang, Zhihua.,Li, Lixin.,Dong, Shishang.,Li, Zhucui.,...&Shui, Wenqing.(2016).Novel Chemical Ligands to Ebola Virus and Marburg Virus Nucleoproteins Identified by Combining Affinity Mass Spectrometry and Metabolomics Approaches.SCIENTIFIC REPORTS,6.
MLA	Fu, Xu,et al."Novel Chemical Ligands to Ebola Virus and Marburg Virus Nucleoproteins Identified by Combining Affinity Mass Spectrometry and Metabolomics Approaches".SCIENTIFIC REPORTS 6(2016).