Structure and inhibition of EV-D68, a virus that causes respiratory illness in children

被引:140
作者
Liu, Yue [1 ]
Sheng, Ju [1 ]
Fokine, Andrei [1 ]
Meng, Geng [1 ]
Shin, Woong-Hee [1 ]
Long, Feng [1 ]
Kuhn, Richard J. [1 ]
Kihara, Daisuke [1 ,2 ]
Rossmann, Michael G. [1 ]
机构
[1] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA
[2] Purdue Univ, Dept Comp Sci, W Lafayette, IN 47907 USA
基金
美国国家卫生研究院;
关键词
HUMAN RHINOVIRUS-14; ENTEROVIRUS; 71; PICORNAVIRUS; PLECONARIL; POLIOVIRUS; RESOLUTION; SUSCEPTIBILITY; ATTACHMENT; SEROTYPES; FEATURES;
D O I
10.1126/science.1261962
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Enterovirus D68 (EV-D68) is a member of Picornaviridae and is a causative agent of recent outbreaks of respiratory illness in children in the United States. We report here the crystal structures of EV-D68 and its complex with pleconaril, a capsid-binding compound that had been developed as an anti-rhinovirus drug. The hydrophobic drug-binding pocket in viral protein 1 contained density that is consistent with a fatty acid of about 10 carbon atoms. This density could be displaced by pleconaril. We also showed that pleconaril inhibits EV-D68 at a half-maximal effective concentration of 430 nanomolar and might, therefore, be a possible drug candidate to alleviate EV-D68 outbreaks.
引用
收藏
页码:71 / 74
页数:4
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