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Researchers identify potential new target for treating hepatitis C
Date:3/29/2010

colleagues, including scientists from Isis Pharmaceuticals Inc., in Carlsbad, Calif., studied a potent small-molecule HCV replication inhibitor called Isis-11 to understand how it inhibits viral replication. They discovered that Isis-11 binds to a region of the viral RNA that is common to all six genotypes of HCV, altering the structure in a way that likely prevents the synthesis of viral proteins. The Isis-11 inhibitor effectively eliminated a bent RNA conformation that other laboratories have shown is required for the proper function of the HCV genomic RNA.

"Binding of Isis-11 resulted in a major conformational change in a specific region of HCV RNA that is thought to be critical for viral replication," says Davis. "This alteration in structure provides a possible mechanism for the antiviral activity of Isis-11 and other HCV replication inhibitors in that chemical class."

It is possible that, because HCV replication inhibitors like Isis-11 bind to a region of RNA that is conserved among all genotypes of the virus, they might be effective against a majority of HCV genotypes. Davis and his colleagues also noted that Isis-11 binds with low affinity to HCV RNA, resulting in a relatively loose bond and suggesting that there is considerable potential for optimizing this class of HCV replication inhibitors by modifying them to have tighter bonds to the genetic material of the virus.

"Now that we know the structure of the inhibitor-found form of the HCV RNA we can use this structure as a basis for a design strategy that will increase the anti-viral activity of these inhibitors," says Davis. "Hopefully, our findings will eventually lead to a new class of highly potent and specific HCV therapeutics."


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Contact: Phil Sahm
phil.sahm@hsc.utah.ed
801-581-2517
University of Utah Health Sciences
Source:Eurekalert

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