Identification and characterization of inhibitors of west nile virus
文献类型:期刊论文
作者 | Puig-Basagoiti, Francesc1; Qing, Min1,2; Dong, Hongping1; Zhang, Bo1; Zou, Gang1,2; Yuan, Zhiming2; Shi, Pei-Yong1,3 |
刊名 | Antiviral research
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出版日期 | 2009-07-01 |
卷号 | 83期号:1页码:71-79 |
关键词 | West nile virus Antiviral drug discovery High-throughput screening Flavivirus replication Rna-dependent rna polymerase Rna cap methyltransferase |
ISSN号 | 0166-3542 |
DOI | 10.1016/j.antiviral.2009.03.005 |
通讯作者 | Shi, pei-yong(pei_yong.shi@novartis.com) |
英文摘要 | Although flaviviruses cause significant human diseases, no antiviral therapy is currently available for clinical treatment of these pathogens. to identify flavivirus inhibitors, we performed a high-throughput screening of compound libraries using cells containing luciferase-reporting replicon of west nile viruses (wnv). five novel small molecular inhibitors of wnv were identified from libraries containing 96,958 compounds. the inhibitors suppress epidemic strain of wnv in cell culture, with ec(50) (50% effective concentration) values of <10 mu m and ti (therapeutic index) values of > 10. viral titer reduction assays, using various flaviviruses and nonflaviviruses, showed that the compounds have distinct antiviral spectra. mode-of-action analysis showed that the inhibitors block distinct steps of wnv replication: four compounds inhibit viral rna syntheses, while the other compound suppresses both viral translation and rna syntheses. biochemical enzyme assays showed that two compounds selectively inhibit viral rna-dependent rna polymerase (rdrp), while another compound specifically inhibits both rdrp and methyltransferase. the identified compounds could potentially be developed for treatment of flavivirus infections. (c) 2009 elsevier b.v. all rights reserved. |
WOS关键词 | JAPANESE ENCEPHALITIS-VIRUS ; SMALL-MOLECULE INHIBITORS ; DEPENDENT RNA-POLYMERASE ; DENGUE-VIRUS ; IN-VITRO ; MONOCLONAL-ANTIBODIES ; VIRAL TRANSLATION ; FLAVIVIRUS INFECTIONS ; MORPHOLINO OLIGOMERS ; BORNE FLAVIVIRUS |
WOS研究方向 | Pharmacology & Pharmacy ; Virology |
WOS类目 | Pharmacology & Pharmacy ; Virology |
语种 | 英语 |
WOS记录号 | WOS:000267480100009 |
出版者 | ELSEVIER SCIENCE BV |
URI标识 | http://www.irgrid.ac.cn/handle/1471x/2375576 |
专题 | 武汉病毒研究所 |
通讯作者 | Shi, Pei-Yong |
作者单位 | 1.New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA 2.Chinese Acad Sci, State Key Lab Virol, Wuhan Inst Virol, Beijing 100864, Peoples R China 3.SUNY Albany, Dept Biomed Sci, Albany, NY USA |
推荐引用方式 GB/T 7714 | Puig-Basagoiti, Francesc,Qing, Min,Dong, Hongping,et al. Identification and characterization of inhibitors of west nile virus[J]. Antiviral research,2009,83(1):71-79. |
APA | Puig-Basagoiti, Francesc.,Qing, Min.,Dong, Hongping.,Zhang, Bo.,Zou, Gang.,...&Shi, Pei-Yong.(2009).Identification and characterization of inhibitors of west nile virus.Antiviral research,83(1),71-79. |
MLA | Puig-Basagoiti, Francesc,et al."Identification and characterization of inhibitors of west nile virus".Antiviral research 83.1(2009):71-79. |
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来源:武汉病毒研究所
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