Bassetto Marcella, Leyssen Pieter, Neyts Johan, Yerukhimovich Mark M, Frick David N, Brancale Andrea
Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff, King Edward VII Avenue, Cardiff CF103NB, UK.
Rega Institute for Medical Research, University of Leuven, Belgium.
Bioorg Med Chem Lett. 2017 Feb 15;27(4):936-940. doi: 10.1016/j.bmcl.2016.12.087. Epub 2017 Jan 3.
A ligand-based approach was applied to screen in silico a library of commercially available compounds, with the aim to find novel inhibitors of the HCV replication starting from the study of the viral NS3 helicase. Six structures were selected for evaluation in the HCV subgenomic replicon assay and one hit was found to inhibit the HCV replicon replication in the low micromolar range. A small series of new pyrrolone compounds was designed and synthesised, and novel structures were identified with improved antiviral activity.
采用基于配体的方法在计算机上筛选市售化合物库，旨在从病毒NS3解旋酶的研究出发寻找丙型肝炎病毒（HCV）复制的新型抑制剂。选择了六种结构在HCV亚基因组复制子试验中进行评估，发现一种活性化合物在低微摩尔范围内可抑制HCV复制子的复制。设计并合成了一小系列新的吡咯烷酮化合物，鉴定出具有改善抗病毒活性的新结构。
