Identification of novel HCV RNA-dependent RNA polymerase inhibitors using pharmacophore-guided virtual screening.
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.
Kim
Jinyoung
J
Department of Bioscience and Biotechnology, Konkuk University, Seoul, Korea.
Kim
Ki-sun
KS
Kim
Dong-Eun
DE
Chong
Youhoon
Y
D000998:Antiviral Agents / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D003198:Computer Simulation; D015195:Drug Design; D016174:Hepacivirus / Q000201:enzymology*; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008968:Molecular Conformation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021281:Quantitative Structure-Activity Relationship; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors* / Q000737:chemistry
D000998:Antiviral Agents; D012324:RNA-Dependent RNA Polymerase