Brief Communication abstract


Nature Chemical Biology 5, 823 - 825 (2009)
Published online: 20 September 2009 | doi:10.1038/nchembio.217

Conformational inhibition of the hepatitis C virus internal ribosome entry site RNA

Jerod Parsons1, M Paola Castaldi1,3, Sanjay Dutta1, Sergey M Dibrov1, David L Wyles2 & Thomas Hermann1

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The internal ribosome entry site (IRES), a highly conserved structured element of the hepatitis C virus (HCV) 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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  1. Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California, USA.
  2. Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
  3. Present address: Makoto Life Sciences, Inc., Bedford, Massachusetts, USA.

Correspondence to: Thomas Hermann1 e-mail: tch@ucsd.edu



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