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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
发表期刊FRONTIERS IN MICROBIOLOGY
卷号8
文章类型Article
摘要Viruses 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.
关键词Hepatitis c Virus Ires Eif3 High Throughput Enhancer Inhibitor
DOI10.3389/fmicb.2017.00977
收录类别SCI
语种英语
WOS记录号WOS:000402243000001
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文献类型期刊论文
版本出版稿
条目标识符http://ir.qdio.ac.cn/handle/337002/137088
专题实验海洋生物学重点实验室
作者单位1.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
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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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