Identification of novel target sites and an inhibitor of the dengue virus E protein

Yennamalli, Ragothaman, Subbarao, Naidu, Kampmann, Thorsten, McGeary, Ross P., Young, Paul R. and Kobe, Bostjan (2009) Identification of novel target sites and an inhibitor of the dengue virus E protein. Journal of Computer-Aided Molecular Design, 23 6: 333-341. doi:10.1007/s10822-009-9263-6

Author Yennamalli, Ragothaman
Subbarao, Naidu
Kampmann, Thorsten
McGeary, Ross P.
Young, Paul R.
Kobe, Bostjan
Title Identification of novel target sites and an inhibitor of the dengue virus E protein
Journal name Journal of Computer-Aided Molecular Design   Check publisher's open access policy
ISSN 0920-654X
Publication date 2009-02-25
Year available 2009
Sub-type Article (original research)
DOI 10.1007/s10822-009-9263-6
Open Access Status Not yet assessed
Volume 23
Issue 6
Start page 333
End page 341
Total pages 9
Editor Andrew R Leach
Federico Gago
Terry R Stouch
Place of publication Netherlands
Publisher Springer - Netherlands
Language eng
Subject C1
030799 Theoretical and Computational Chemistry not elsewhere classified
970106 Expanding Knowledge in the Biological Sciences
Abstract Dengue and related flaviviruses represent a significant global health threat. The envelope glycoprotein E mediates virus attachment to a host cell and the subsequent fusion of viral and host cell membranes. The fusion process is driven by conformational changes in the E protein and is an essential step in the virus life cycle. In this study, we analyzed the pre-fusion and post-fusion structures of the dengue virus E protein to identify potential novel sites that could bind small molecules, which could interfere with the conformational transitions that mediate the fusion process. We used an in silico virtual screening approach combining three different docking algorithms (DOCK, GOLD and FlexX) to identify compounds that are likely to bind to these sites. Seven structurally diverse molecules were selected to test experimentally for inhibition of dengue virus propagation. The best compound showed an IC(50) in the micromolar range against dengue virus type 2.
Keyword Dengue virus
Envelope protein
Virtual drug screening
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Chemistry and Molecular Biosciences
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Citation counts: TR Web of Science Citation Count  Cited 38 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 42 times in Scopus Article | Citations
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Created: Thu, 03 Sep 2009, 18:06:41 EST by Mr Andrew Martlew on behalf of School of Chemistry & Molecular Biosciences