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Chinese Academy of Sciences Institutional Repositories Grid
Identification of a novel inhibitor against middle east respiratory syndrome coronavirus

文献类型:期刊论文

作者Sun, Yaping1,2; Zhang, Huaidong1; Shi, Jian1; Zhang, Zhe1; Gong, Rui1
刊名Viruses-basel
出版日期2017-09-01
卷号9期号:9页码:12
关键词Mers-cov Fusion inhibitor Six-helix bundle Heptad repeat Five-helix bundle
ISSN号1999-4915
DOI10.3390/v9090255
通讯作者Gong, rui(gongr@wh.iov.cn)
英文摘要The middle east respiratory syndrome coronavirus (mers-cov) was first isolated in 2012, and circulated worldwide with high mortality. the continual outbreaks of mers-cov highlight the importance of developing antiviral therapeutics. here, we rationally designed a novel fusion inhibitor named mers-five-helix bundle (mers-5hb) derived from the six-helix bundle (mers-6hb) which was formed by the process of membrane fusion. mers-5hb consists of three copies of heptad repeat 1 (hr1) and two copies of heptad repeat 2 (hr2) while mers-6hb includes three copies each of hr1 and hr2. as it lacks one hr2, mers-5hb was expected to interact with viral hr2 to interrupt the fusion step. what we found was that mers-5hb could bind to hr2p, a peptide derived from hr2, with a strong affinity value (k-d) of up to 0.24 nm. subsequent assays indicated that mers-5hb could inhibit pseudotyped mers-cov entry effectively with 50% inhibitory concentration (ic50) of about 1 mu m. in addition, mers-5hb significantly inhibited spike (s) glycoprotein-mediated syncytial formation in a dose-dependent manner. further biophysical characterization showed that mers-5hb was a thermo-stable alpha-helical secondary structure. the inhibitory potency of mers-5hb may provide an attractive basis for identification of a novel inhibitor against mers-cov, as a potential antiviral agent.
WOS关键词RECEPTOR-BINDING DOMAIN ; MERS-COV ; SPIKE PROTEIN ; NEUTRALIZING ANTIBODIES ; SAUDI-ARABIA ; SUBUNIT VACCINES ; S PROTEIN ; FUSION ; PEPTIDE ; ENTRY
WOS研究方向Virology
WOS类目Virology
语种英语
WOS记录号WOS:000411491600011
出版者MDPI AG
URI标识http://www.irgrid.ac.cn/handle/1471x/2373387
专题武汉病毒研究所
通讯作者Gong, Rui
作者单位1.Chinese Acad Sci, Ctr Emerging Infect Dis, CAS Key Lab Special Pathogens & Biosafety, Wuhan Inst Virol, 44 Xiao Hong Shan, Wuhan 430071, Hubei, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
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Sun, Yaping,Zhang, Huaidong,Shi, Jian,et al. Identification of a novel inhibitor against middle east respiratory syndrome coronavirus[J]. Viruses-basel,2017,9(9):12.
APA Sun, Yaping,Zhang, Huaidong,Shi, Jian,Zhang, Zhe,&Gong, Rui.(2017).Identification of a novel inhibitor against middle east respiratory syndrome coronavirus.Viruses-basel,9(9),12.
MLA Sun, Yaping,et al."Identification of a novel inhibitor against middle east respiratory syndrome coronavirus".Viruses-basel 9.9(2017):12.

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来源:武汉病毒研究所

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