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Design and characterization of viral polypeptide inhibitors targeting newcastle disease virus fusion
Zhu, JQ; Jiang, XL; Liu, YY; Tien, P; Gao, GF
刊名Journal of molecular biology
2005-12-02
卷号354期号:3页码:601-613
关键词Inhibitors design Fusion Heptad repeat (hr) Paramyxovirus Newcastle disease virus (ndv)
ISSN号0022-2836
DOI10.1016/j.jmb.2005.08.078
通讯作者Tien, p()
英文摘要Paramyxovirus infections can be detected worldwide with some emerging zoonotic viruses and currently there are no specific therapeutic treatments or vaccines available for many of these diseases. recent studies have demonstrated that pepticies derived from the two heptad repeat regions (hr1 and hr2) of paramyxovirus fusion proteins could be used as inhibitors of virus fusion. the mechanism underlying this activity is in accordance with that of class i virus fusion proteins, of which human immunodeficiency virus (hiv) and influenza virus fusion proteins are members. for class i virus fusion proteins, the hr1 fragment binds to hr2 to form a six-helix bundle with three hr1 fragments forming the central coiled bundle surrounded by three coiled hr2 fragments in the post fusion conformational state (fusion core). it is hypothesized that the introduced exogenous hr1. or hr2 can compete against their endogenous counterparts, which results in fusion inhibition. using newcastle disease virus (ndv) as a model, we designed several protein inhibitors, denoted hr212 as well ashr121 and 5-helix, which could bind the hr1 or hr2 region of fusion protein, respectively. all the proteins were expressed and purified using a gst-fusion expression system in escherichia coli. the hr212 or gst-hr212 protein, which binds the hr1 peptide in vitro, displayed inhibitory activity against ndv-mediated cell fusion, while the hr121 and 5-helix proteins, which bind the hr2 peptide in vitro, inhibited virus fusion from the avirulent ndv strain when added before the cleavage of the fusion protein. these results showed that the designed hr212, hr121 or 5-helix protein could serve as specific antiviral agents. these data provide additional insight into the difference between the virulent and avirulent strains of ndv. (c) 2005 published by elsevier ltd.
WOS关键词HEPTAD REPEAT REGIONS ; PARAMYXOVIRUS FUSION ; MEMBRANE-FUSION ; MEASLES-VIRUS ; F-PROTEINS ; PEPTIDE INHIBITOR ; POTENT INHIBITORS ; 6-HELIX BUNDLE ; HIV-1 ENTRY ; CELL-FUSION
WOS研究方向Biochemistry & Molecular Biology
WOS类目Biochemistry & Molecular Biology
语种英语
出版者ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
WOS记录号WOS:000233674100010
内容类型期刊论文
URI标识http://www.corc.org.cn/handle/1471x/2377456
专题中国科学院大学
通讯作者Tien, P
作者单位1.Chinese Acad Sci, Inst Microbiol, Ctr Mol Virol, Beijing 100080, Peoples R China
2.Chinese Acad Sci, Grad Sch, Beijing 100049, Peoples R China
3.Chinese Ctr Dis Control & Prevent, Dept Diarrhea Viruses, Inst Viral Dis Control & Prevent China CDC, Beijing 100052, Peoples R China
4.Zhejiang Univ, Coll Life Sci, Inst Microbiol, Hangzhou 310029, Peoples R China
推荐引用方式
GB/T 7714
Zhu, JQ,Jiang, XL,Liu, YY,et al. Design and characterization of viral polypeptide inhibitors targeting newcastle disease virus fusion[J]. Journal of molecular biology,2005,354(3):601-613.
APA Zhu, JQ,Jiang, XL,Liu, YY,Tien, P,&Gao, GF.(2005).Design and characterization of viral polypeptide inhibitors targeting newcastle disease virus fusion.Journal of molecular biology,354(3),601-613.
MLA Zhu, JQ,et al."Design and characterization of viral polypeptide inhibitors targeting newcastle disease virus fusion".Journal of molecular biology 354.3(2005):601-613.
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