Identification of serotonin 2a receptor as a novel hcv entry factor by a chemical biology strategy
文献类型：期刊论文
| 作者 | Cao, Lin1,2,5,6; Chen, Jizheng4; Wang, Yaxin1,2,3,5,6; Yang, Yuting7; Qing, Jie5,6; Rao, Zihe1,2,3,5,6; Chen, Xinwen4; Lou, Zhiyong5,6 |
| 刊名 | Protein & cell
 |
| 出版日期 | 2019-03-01 |
| 卷号 | 10期号:3页码:178-195 |
| ISSN号 | 1674-800X |
| 关键词 | Hcv Serotonin 2a receptor Entry Antiviral drug |
| DOI | 10.1007/s13238-018-0521-z |
| 通讯作者 | Chen, xinwen(chenxw@wh.iov.cn) ; Lou, zhiyong(louzy@mail.tsinghua.edu.cn) |
| 英文摘要 | Hepatitis c virus (hcv) is a leading cause of liver disease worldwide. although several hcv protease/polymerase inhibitors were recently approved by u.s. fda, the combination of antivirals targeting multiple processes of hcv lifecycle would optimize anti-hcv therapy and against potential drug-resistance. viral entry is an essential target step for antiviral development, but fda-approved hcv entry inhibitor remains exclusive. here we identify serotonin 2a receptor (5-ht2ar) is a hcv entry factor amendable to therapeutic intervention by a chemical biology strategy. the silencing of 5-ht2ar and clinically available 5-ht2ar antagonist suppress cell culture-derived hcv (hcvcc) in different liver cells and primary human hepatocytes at late endocytosis process. the mechanism is related to regulate the correct plasma membrane localization of claudin 1 (cldn1). moreover, phenoxybenzamine (pbz), an fda-approved 5-ht2ar antagonist, inhibits all major hcv genotypes in vitro and displays synergy in combination with clinical used anti-hcv drugs. the impact of pbz on hcv genotype 2a is documented in immune-competent humanized transgenic mice. our results not only expand the understanding of hcv entry, but also present a promising target for the invention of hcv entry inhibitor. |
| WOS关键词 | HEPATITIS-C VIRUS ; PROTEIN-KINASE-C ; APOLIPOPROTEIN-E ; B-VIRUS ; L-SIGN ; BINDING ; 5-HYDROXYTRYPTAMINE ; REACTIVATION ; ANTAGONISTS ; INHIBITOR |
| WOS研究方向 | Cell Biology |
| WOS类目 | Cell Biology |
| 语种 | 英语 |
| 出版者 | SPRINGEROPEN |
| WOS记录号 | WOS:000456279800003 |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2373202 |
| 专题 | 武汉病毒研究所 |
| 通讯作者 | Chen, Xinwen; Lou, Zhiyong |
| 作者单位 | 1.Nankai Univ, Coll Pharm, Tianjin 300071, Peoples R China 2.Nankai Univ, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China 3.Chinese Acad Sci, Inst Biophys, Natl Lab Macromol, Beijing 100101, Peoples R China 4.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Hubei, Peoples R China 5.Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China 6.Tsinghua Univ, Collaborat Innovat Ctr Biotherapy, Beijing 100084, Peoples R China 7.Beijing 166 High Sch, Beijing 100006, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cao, Lin,Chen, Jizheng,Wang, Yaxin,et al. Identification of serotonin 2a receptor as a novel hcv entry factor by a chemical biology strategy[J]. Protein & cell,2019,10(3):178-195. |
| APA | Cao, Lin.,Chen, Jizheng.,Wang, Yaxin.,Yang, Yuting.,Qing, Jie.,...&Lou, Zhiyong.(2019).Identification of serotonin 2a receptor as a novel hcv entry factor by a chemical biology strategy.Protein & cell,10(3),178-195. |
| MLA | Cao, Lin,et al."Identification of serotonin 2a receptor as a novel hcv entry factor by a chemical biology strategy".Protein & cell 10.3(2019):178-195. |
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来源：武汉病毒研究所
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