Identification of Novel HCV RNA‐dependent RNA polymerase Inhibitors Using Pharmacophore‐Guided Virtual Screening
Jinyoung Kim, Ki-Sun Kim, Dong‐Eun Kim, Youhoon Chong · Chemical Biology & Drug Design · 2008
We performed pharmacophore-guided virtual screening experiments using FlexX-Pharm to identify novel inhibitors of hepatitis C virus RNA-dependent RNA polymerase. Pharmacophore model generated from our previous analysis of the binding modes as well as structure-based three-dimensional quantitative structure-activity relationship studies of aryl diketoacid analogues was used. In pharmacophore-guided virtual screening study, among 37 447 compounds in LeadQuest chemical library, 40 compounds were selected as novel candidates of hepatitis C virus RNA-dependent RNA polymerase inhibitors, and their biological activities were evaluated. Especially, T29 was chosen for further development.