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Vertex Pharmaceuticals Researchers Report Three-Dimensional Structure Of Hepatitis C Helicase Enzyme; Report In Structure

Cambridge, MA, January 15, 1998 -- Researchers from Vertex Pharmaceuticals Incorporated have solved the three-dimensional atomic structure of the hepatitis C virus NS3 helicase, an enzyme that plays a key role in viral replication. The achievement is described in a paper, "Hepatitis C Virus NS3 RNA Helicase Domain with a Bound Oligonucleotide: The Crystal Structure Provides Insights into the Mode of Unwinding," published in the January 15, 1998 issue of the journal Structure. The publication follows the presentation of the helicase structure at the Second International Conference on Therapies for Viral Hepatitis in Kona, Hawaii, in December 1997. Vertex is using the structural information to design hepatitis C helicase inhibitors as new antiviral drugs to treat hepatitis C virus (HCV) infection.

"This paper presents for the first time detailed information on the critical interaction between the hepatitis C helicase and viral RNA," said Dr. Joseph L. Kim, Vertex crystallographer and an author of the Structure paper. "The nucleic acid binding site of the helicase enzyme, as well as the previously described nucleoside triphosphate (NTP) binding site, are attractive targets for disrupting this interaction. These two targets, which comprise the active sites of the helicase enzyme, are a focus of our ongoing drug design efforts."

Helicases are enzymes distinguished by their ability to unwind regions of double-stranded RNA or DNA, in preparation for replication or transcription of genetic information. In the case of hepatitis C, the NS3 helicase functions to unwind double-stranded viral RNA complexes. The resulting RNA strands then serve as templates for the synthesis of more RNA or for translation into protein. Alternately, the new RNA may be packaged into new virus particles, which are released from cells to propagate infection.

Vertex scientists determined the three-dimensional structure of h
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Contact: Michael Partridge
partridge@vpharm.com
(617) 577-6108
Vertex Pharmaceuticals
15-Jan-1998


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