Abstract: The invention features methods and compositions for screening for agents that modulate replication of a virus, particularly Flaviviridae virus (particularly hepatitis C virus (HCV)), where the methods provide for detection of agents that modulate the binding of TBC and NS5A, the inhibition of TBC activity, inhibition of Rab1 activity, and/or the expression of the TBC protein and/or Rab1 protein. The invention also features methods of controlling viral replication, and agents useful in such methods.

Abstract: The invention features methods and compositions for screening for agents that modulate replication of a virus, particularly Flaviviridae virus (particularly hepatitis C virus (HCV)), where the methods provide for detection of agents that modulate the binding of TBC and NS5A, the inhibition of TBC activity, inhibition of Rab1 activity, and/or the expression of the TBC protein and/or Rab1 protein. The invention also features methods of controlling viral replication, and agents useful in such methods.

Abstract: An amphipathic helix at the approximate N-terminus of Hepatitis C virus (HCV) nonstructural proteins mediates the association of these proteins with cytoplasmic membranes in infected cells. This association is essential for replication. Thus, assessing the ability of compounds or protocols to disrupt the association of such helices with cytoplasmic membranes permits identification of compounds and protocols which are useful in the treatment of HCV infection. Also useful in the invention are mimics, or function-disrupting ligands, of an amphipathic helix of the nonstructural proteins described herein and antibodies and fragments thereof immunoreactive with said helix.