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

doi:10.1038/srep29680

	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, Wenqing6
	2016-07-12
发表期刊	SCIENTIFIC REPORTS
ISSN	2045-2322
卷号	6
发表状态	已发表
DOI	10.1038/srep29680
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.
收录类别	SCI
语种	英语
资助项目	National Science and Technology Major Projects for "Major New Drug Innovation and Development"[2015ZX09J15102-004-004]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000379389600002
出版者	NATURE PUBLISHING GROUP
WOS关键词	XANTHINE-OXIDASE ; LC-MS ; ULTRAFILTRATION ; INHIBITORS ; RNA ; GLYCYRRHIZIN ; REPLICATION ; DISEASE ; COMPLEX ; CHROMATOGRAPHY
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1779
专题	iHuman研究所_PI研究组_水雯箐组
通讯作者	Wang, Yuefei; Shui, Wenqing
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
通讯作者单位	上海科技大学
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).