Slow binding inhibition and mechanism of resistance of non-nucleoside polymerase inhibitors of hepatitis C virus.

@article{Hang2009SlowBI,
  title={Slow binding inhibition and mechanism of resistance of non-nucleoside polymerase inhibitors of hepatitis C virus.},
  author={Julie Qi Hang and Yanli Yang and Seth F. Harris and Vincent J-P L{\'e}v{\^e}que and Hannah J. Whittington and Sonal Rajyaguru and Gloria Ao-Ieong and Matthew F. McCown and April Sum Y Wong and Anthony M. Giannetti and Sophie Le Pogam and Francisco X Talamas and Nick Cammack and Isabel N{\'a}jera and Klaus Klumpp},
  journal={The Journal of biological chemistry},
  year={2009},
  volume={284 23},
  pages={15517-29}
}
The binding affinity of four palm and thumb site representative non-nucleoside inhibitors (NNIs) of HCV polymerase NS5B to wild-type and resistant NS5B polymerase proteins was determined, and the influence of RNA binding on NNI binding affinity was investigated. NNIs with high binding affinity potently inhibited HCV RNA polymerase activity and replicon replication. Among the compounds tested, HCV-796 showed slow binding kinetics to NS5B. The binding affinity of HCV-796 to NS5B increased 27-fold… CONTINUE READING