Team tackles new approach to halting hep C replication

Binding a potent inhibitor of the hepatitis C virus to the genetic material of the virus may halt replication, according to a team of scientists at work on the approach. Their work, published in the March 29 early edition of the Proceedings of the National Academy of Sciences, offers a new target for the structure-based design of hepatitis C treatments.

"The available therapies for hepatitis C infection have limited effectiveness, with less than a 50 percent response," says Darrell Davis, Ph.D., the lead author and professor and interim chair of medicinal chemistry and professor of biochemistry at the University of Utah. "However, small molecules that inhibit viral replication have been reported and they represent potential opportunities for new, more effective HCV treatments."

The team focused on an inhibitor dubbed Isis-11, finding that it binds to a region of the viral RNA that is common to all six genotypes of HCV and 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."

- here's the press release for more info