Mutations in the hepatitis C virus polymerase that increase RNA binding can confer resistance to cyclosporine A.

ABSTRACT:

Unlabelled

Hepatitis C virus (HCV) infection leads to acute and chronic liver diseases, and new classes of anti-HCV therapeutics are needed. Cyclosporine A (CsA) inhibits HCV replication and CsA derivatives that lack the immunosuppressive function are currently in clinical trials as candidate anti-HCV drugs. Here we characterize several independently derived HCV replicons with varying levels of CsA resistance due to mutations in nonstructural protein 5B (NS5B), the HCV-encoded polymerase. Mutant HCV replicons engineered with these mutations showed resistance to CsA. The mutations reside in two distinct patches in the polymerase: the template channel and one face of a concave surface behind the template channel. Mutant NS5B made by cells expressing the HCV replicon had increased abi

SUBMITTER: Liu Z 

PROVIDER: S-EPMC2727352 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature