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

2009; Nature Portfolio; Volume: 5; Issue: 11 Linguagem: Inglês

10.1038/nchembio.217

1552-4469

Jerod Parsons, M. Paola Castaldi, Sanjay Dutta, Sergey M. Dibrov, David Wyles, Thomas Hermann,

RNA and protein synthesis mechanisms

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.