Discovery of flavonoid derivatives as anti-HCV agents via pharmacophore search combining molecular docking strategy

Common feature based pharmacophore and structure-based docking approaches have been employed in the identification of novel anti-HCV candidates from our in-house database. A total of 31 hits identified in silico were screened in vitro assay. 20 Compounds demonstrated anti-HCV activities (EC50 < 50 μM), including two naturally occurring flavones apigenin (21) and luteolin (22) with low micromole EC50 values and three compounds (23, 24 and 25) of novel scaffolds with moderate potencies. In addition, pharmacophore refinement was also conducted based on the current knowledge of flavone-derived anti-HCV candidates and the results of combined in silico and in vitro assays.

Graphical abstractCombined pharmacophore and structure-based approaches were employed in screening novel anti-HCV candidates and 20 compounds were found to be active in vitro including two naturally occurring flavones.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► The HipHop pharmacophore model was generated for NS5B inhibitors. ► Virtual screening was performed based on both pharmacophore and docking models. ► Several selected compounds were discovered to possess anti-HCV activities.