The inventors have discovered that an ATPase-deficient dominant-negative
mutant NS3 protein of hepatitis C virus inhibits activity of the
wild-type NS3 protein and inhibits replication of hepatitis C virus
(HCV). The solved crystal structure of a multi-enzyme NS3 complex on a
DNA substrate is also provided. The inventors have tested a peptide
matching the sequence of a portion of NS3 that interacts with another NS3
molecule for inhibiting HCV replication. The peptide inhibits HCV
replication. Accordingly, the invention provides a method of inhibiting
HCV replication in cells infected with HCV involving transforming the
cells with a vector expressing a dominant-negative mutant NS3 gene. The
invention also provides a method of inhibiting HCV replication in cells
infected with HCV involving administering to the cells a
dominant-negative mutant NS3 protein. The invention also provides
peptides and agents that inhibit HCV replication and methods of
identifying agents that inhibit HCV replication.