Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Antiviral Agents / pharmacology
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Antiviral Agents / therapeutic use
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Base Sequence
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Benzimidazoles / pharmacology
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Cytosine / chemistry
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Genome, Viral / drug effects
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Genotype
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Hepacivirus / chemistry
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Hepacivirus / drug effects
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Hepacivirus / genetics
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Hepacivirus / metabolism*
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Magnesium / pharmacology
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Models, Molecular
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Nucleic Acid Conformation
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RNA, Viral / chemistry
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RNA, Viral / genetics
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RNA, Viral / metabolism
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Replicon / drug effects
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Replicon / genetics
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Ribosomes / genetics
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Ribosomes / metabolism*
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Ribosomes / virology
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Signal Transduction
Substances
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Antiviral Agents
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Benzimidazoles
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RNA, Viral
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Cytosine
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Magnesium
Associated data
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PubChem-Substance/85182175
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PubChem-Substance/85182176
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PubChem-Substance/85182177
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PubChem-Substance/85182178
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PubChem-Substance/85182179