Conformational inhibition of the HCV IRES RNA

The internal ribosome entry site (IRES), a highly conserved structured element of the hepatitis C virus genomic RNA, is an attractive target for antiviral drugs. Here we show that benzimidazole inhibitors of the HCV replicon act by conformational induction of a widened interhelical angle in the IRES...

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Autores principales: Parsons, Jerod, Castaldi, M. Paola, Dutta, Sanjay, Dibrov, Sergey M., Wyles, David L., Hermann, Thomas
Formato: Texto
Lenguaje:English
Publicado: 2009
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2770845/
https://www.ncbi.nlm.nih.gov/pubmed/19767736
http://dx.doi.org/10.1038/nchembio.217
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author Parsons, Jerod
Castaldi, M. Paola
Dutta, Sanjay
Dibrov, Sergey M.
Wyles, David L.
Hermann, Thomas
author_facet Parsons, Jerod
Castaldi, M. Paola
Dutta, Sanjay
Dibrov, Sergey M.
Wyles, David L.
Hermann, Thomas
author_sort Parsons, Jerod
collection PubMed
description The internal ribosome entry site (IRES), a highly conserved structured element of the hepatitis C virus genomic RNA, is an attractive target for antiviral drugs. Here we show that benzimidazole inhibitors of the HCV replicon act by conformational induction of a widened interhelical angle in the IRES subdomain IIa which facilitates the undocking of subdomain IIb from the ribosome and ultimately leads to inhibition of IRES-driven translation in HCV-infected cells.
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spelling pubmed-27708452010-05-01 Conformational inhibition of the HCV IRES RNA Parsons, Jerod Castaldi, M. Paola Dutta, Sanjay Dibrov, Sergey M. Wyles, David L. Hermann, Thomas Nat Chem Biol Article The internal ribosome entry site (IRES), a highly conserved structured element of the hepatitis C virus genomic RNA, is an attractive target for antiviral drugs. Here we show that benzimidazole inhibitors of the HCV replicon act by conformational induction of a widened interhelical angle in the IRES subdomain IIa which facilitates the undocking of subdomain IIb from the ribosome and ultimately leads to inhibition of IRES-driven translation in HCV-infected cells. 2009-09-20 2009-11 /pmc/articles/PMC2770845/ /pubmed/19767736 http://dx.doi.org/10.1038/nchembio.217 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Parsons, Jerod
Castaldi, M. Paola
Dutta, Sanjay
Dibrov, Sergey M.
Wyles, David L.
Hermann, Thomas
Conformational inhibition of the HCV IRES RNA
title Conformational inhibition of the HCV IRES RNA
title_full Conformational inhibition of the HCV IRES RNA
title_fullStr Conformational inhibition of the HCV IRES RNA
title_full_unstemmed Conformational inhibition of the HCV IRES RNA
title_short Conformational inhibition of the HCV IRES RNA
title_sort conformational inhibition of the hcv ires rna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2770845/
https://www.ncbi.nlm.nih.gov/pubmed/19767736
http://dx.doi.org/10.1038/nchembio.217
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