An in silico virtual screening study for the design of norovirus inhibitors: fragment-based molecular docking and binding free energy calculations

Gastrointestinal infections caused by noroviruses may be prevented by the inhibition of their binding to histo-blood group carbohydrate antigens. A fragment-based virtual screening approach was used, employing docking followed by molecular dynamics simulations in order to enable binding free energy calculations using the linear interaction energy method. The resulting structures, composed of high-affinity fragments, can be a good starting point for lead optimizations and four molecules that pass both REOS and SYLVIA filters, which can remove known toxic features and assess the synthetic accessibility, respectively, are proposed as inhibitors.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights•Infections caused by noroviruses may be prevented by the inhibition of their binding to histoblood group carbohydrate antigens.•A fragment-based virtual screening approach was used to find building blocks.•Molecular structures that can be good starting points for lead optimizations are proposed.