In vitro selection and characterization of hepatitis C virus serine protease variants resistant to an active-site peptide inhibitor.

ABSTRACT: The hepatitis C virus (HCV) serine protease is necessary for viral replication and represents a valid target for developing new therapies for HCV infection. Potent and selective inhibitors of this enzyme have been identified and shown to inhibit HCV replication in tissue culture. The optimization of these inhibitors for clinical development would greatly benefit from in vitro systems for the identification and the study of resistant variants. We report the use HCV subgenomic replicons to isolate and characterize mutants resistant to a protease inhibitor. Taking advantage of the replicons' ability to transduce resistance to neomycin, we selected replicons with decreased sensitivity to the inhibitor by culturing the host cells in the presence of the inhibitor and neomycin. The selected repli

SUBMITTER: Trozzi C 

PROVIDER: S-EPMC149541 | biostudies-literature | 2003 Mar

REPOSITORIES: biostudies-literature