BACKGROUND: Despite the great progress made in the last 10 years, alternative strategies might help improving definitive treatment options against hepatitis C virus infection. METHODS: With the aim of identifying novel inhibitors of the hepatitis C virus-1b replication targeting the viral NS3 helicase, the structures of previously reported symmetrical inhibitors of this enzyme were rationally modified, and according to docking-based studies, four novel scaffolds were selected for synthesis and evaluation in the hepatitis C virus-1b subgenomic replicon assay. RESULTS: Among the newly designed compounds, one new structural family was found to inhibit the hepatitis C virus-1b replication in the micromolar range. This scaffold was chosen for further exploration and different novel analogues were synthesised and evaluated. CONCLUSIONS: Different new inhibitors of the hepatitis C virus genotype 1b replication were identified. Some of the new compounds show mild inhibition of the NS3 helicase enzyme.
BACKGROUND: Despite the great progress made in the last 10 years, alternative strategies might help improving definitive treatment options against hepatitis C virus infection. METHODS: With the aim of identifying novel inhibitors of the hepatitis C virus-1b replication targeting the viral NS3 helicase, the structures of previously reported symmetrical inhibitors of this enzyme were rationally modified, and according to docking-based studies, four novel scaffolds were selected for synthesis and evaluation in the hepatitis C virus-1b subgenomic replicon assay. RESULTS: Among the newly designed compounds, one new structural family was found to inhibit the hepatitis C virus-1b replication in the micromolar range. This scaffold was chosen for further exploration and different novel analogues were synthesised and evaluated. CONCLUSIONS: Different new inhibitors of the hepatitis C virus genotype 1b replication were identified. Some of the new compounds show mild inhibition of the NS3 helicase enzyme.
Authors: Patrick D Morris; Alicia K Byrd; Alan J Tackett; Craig E Cameron; Poonam Tanega; Robert Ott; Ellen Fanning; Kevin D Raney Journal: Biochemistry Date: 2002-02-19 Impact factor: 3.162
Authors: J L Kim; K A Morgenstern; J P Griffith; M D Dwyer; J A Thomson; M A Murcko; C Lin; P R Caron Journal: Structure Date: 1998-01-15 Impact factor: 5.006
Authors: William R Shadrick; Sourav Mukherjee; Alicia M Hanson; Noreena L Sweeney; David N Frick Journal: Biochemistry Date: 2013-08-26 Impact factor: 3.162