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Establishment and Application of a High Throughput Screening System Targeting the Interaction between HCV Internal Ribosome Entry Site and Human Eukaryotic Translation Initiation Factor 3
Zhu, Yuying1,2,3; Huang, Pei4; Yang, Na1,2; Liu, Rui1,2; Liu, Xueting4; Dai, Huanqin4; Zhang, Lixin4,5; Song, Fuhang4; Sun, Chaomin1,2
2017-05-29
Source PublicationFRONTIERS IN MICROBIOLOGY
Volume8
SubtypeArticle
AbstractViruses are intracellular obligate parasites and the host cellular machinery is usually recruited for their replication. Human eukaryotic translation initiation factor 3 (eIF3) could be directly recruited by the hepatitis C virus (HCV) internal ribosome entry site (IRES) to promote the translation of viral proteins. In this study, we establish a fluorescence polarization (FP) based high throughput screening (HTS) system targeting the interaction between HCV IRES and eIF3. By screening a total of 894 compounds with this HTS system, two compounds (Mucl39526 and NP39) are found to disturb the interaction between HCV IRES and eIF3. And these two compounds are further demonstrated to inhibit the HCV IRES-dependent translation in vitro. Thus, this HTS system is functional to screen the potential HCV replication inhibitors targeting human eIF3, which is helpful to overcome the problem of viral resistance. Surprisingly, one compound HP-3, a kind of oxytocin antagonist, is discovered to significantly enhance the interaction between HCV IRES and eIF3 by this HTS system. HP-3 is demonstrated to directly interact with HCV IRES and promote the HCV IRES-dependent translation both in vitro and in vivo, which strongly suggests that HP-3 has potentials to promote HCV replication. Therefore, this HTS system is also useful to screen the potential HCV replication enhancers, which is meaningful for understanding the viral replication and screening novel antiviral drugs. To our knowledge, this is the first HTS system targeting the interaction between eIF3 and HCV IRES, which could be applied to screen both potential HCV replication inhibitors and enhancers.
KeywordHepatitis c Virus Ires Eif3 High Throughput Enhancer Inhibitor
DOI10.3389/fmicb.2017.00977
Indexed BySCI
Language英语
WOS IDWOS:000402243000001
Citation statistics
Cited Times:2[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Version出版稿
Identifierhttp://ir.qdio.ac.cn/handle/337002/137088
Collection实验海洋生物学重点实验室
Affiliation1.Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao, Peoples R China
2.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Biol & Biotechnol, Qingdao, Peoples R China
3.Univ Chinese Acad Sci, Coll Earth Sci, Beijing, Peoples R China
4.Chinese Acad Sci, Inst Microbiol, Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China
5.East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China
First Author AffilicationInstitute of Oceanology, Chinese Academy of Sciences
Recommended Citation
GB/T 7714
Zhu, Yuying,Huang, Pei,Yang, Na,et al. Establishment and Application of a High Throughput Screening System Targeting the Interaction between HCV Internal Ribosome Entry Site and Human Eukaryotic Translation Initiation Factor 3[J]. FRONTIERS IN MICROBIOLOGY,2017,8.
APA Zhu, Yuying.,Huang, Pei.,Yang, Na.,Liu, Rui.,Liu, Xueting.,...&Sun, Chaomin.(2017).Establishment and Application of a High Throughput Screening System Targeting the Interaction between HCV Internal Ribosome Entry Site and Human Eukaryotic Translation Initiation Factor 3.FRONTIERS IN MICROBIOLOGY,8.
MLA Zhu, Yuying,et al."Establishment and Application of a High Throughput Screening System Targeting the Interaction between HCV Internal Ribosome Entry Site and Human Eukaryotic Translation Initiation Factor 3".FRONTIERS IN MICROBIOLOGY 8(2017).
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