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

Yue Liu | Zendy; Ju Sheng | Zendy; Andrei Fokine | Zendy; Geng Meng | Zendy; WoongHee Shin | Zendy; Feng Long | Zendy; Richard Kühn | Zendy; Daisuke Kihara | Zendy; Michael G. Rossmann | Zendy

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

Author(s) -

Yue Liu,

Ju Sheng,

Andrei Fokine,

Geng Meng,

WoongHee Shin,

Feng Long,

Richard Kühn,

Daisuke Kihara,

Michael G. Rossmann

Publication year - 2015

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.1261962

Subject(s) - rhinovirus , capsid , outbreak , virology , respiratory illness , antiviral drug , chemistry , drug , virus , enterovirus , respiratory system , biology , medicine , pharmacology

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.

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