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

Abstract

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 in this paper 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. Finally, 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.

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [1];  [2];  [1]
  1. Purdue Univ., West Lafayette, IN (United States). Hockmeyer Hall of Structural Biology. Dept. of Biological Sciences
  2. Purdue Univ., West Lafayette, IN (United States). Hockmeyer Hall of Structural Biology. Dept. of Biological Sciences. Dept. of Computer Science
Publication Date:
Research Org.:
Purdue Univ., West Lafayette, IN (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Inst. of Health (NIH) (United States)
OSTI Identifier:
1168487
Grant/Contract Number:  
AC02-06CH11357; RR007707; AI11219
Resource Type:
Accepted Manuscript
Journal Name:
Science
Additional Journal Information:
Journal Volume: 347; Journal Issue: 6217; Journal ID: ISSN 0036-8075
Publisher:
AAAS
Country of Publication:
United States
Language:
ENGLISH
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Liu, Yue, Sheng, Ju, Fokine, Andrei, Meng, Geng, Shin, Woong-Hee, Long, Feng, Kuhn, Richard J., Kihara, Daisuke, and Rossmann, Michael G. Structure and inhibition of EV-D68, a virus that causes respiratory illness in children. United States: N. p., 2015. Web. doi:10.1126/science.1261962.
Liu, Yue, Sheng, Ju, Fokine, Andrei, Meng, Geng, Shin, Woong-Hee, Long, Feng, Kuhn, Richard J., Kihara, Daisuke, & Rossmann, Michael G. Structure and inhibition of EV-D68, a virus that causes respiratory illness in children. United States. doi:10.1126/science.1261962.
Liu, Yue, Sheng, Ju, Fokine, Andrei, Meng, Geng, Shin, Woong-Hee, Long, Feng, Kuhn, Richard J., Kihara, Daisuke, and Rossmann, Michael G. Fri . "Structure and inhibition of EV-D68, a virus that causes respiratory illness in children". United States. doi:10.1126/science.1261962. https://www.osti.gov/servlets/purl/1168487.
@article{osti_1168487,
title = {Structure and inhibition of EV-D68, a virus that causes respiratory illness in children},
author = {Liu, Yue and Sheng, Ju and Fokine, Andrei and Meng, Geng and Shin, Woong-Hee and Long, Feng and Kuhn, Richard J. and Kihara, Daisuke and Rossmann, Michael G.},
abstractNote = {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 in this paper 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. Finally, 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.},
doi = {10.1126/science.1261962},
journal = {Science},
number = 6217,
volume = 347,
place = {United States},
year = {2015},
month = {1}
}

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