title: An in silico virtual screening study for the design of norovirus inhibitors: fragment-based molecular docking and binding free energy calculations.
abstract: 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.
authors.affiliation: Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, S-106 91 Stockholm, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Lundborg
authors.forename: Eunus
authors.initials: E
authors.lastname: Ali
authors.forename: Göran
authors.initials: G
authors.lastname: Widmalm
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D019295:Computational Biology; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D029322:Norovirus / Q000187:drug effects* / Q000378:metabolism; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics; D014584:User-Computer Interface
chemical_list: D000998:Antiviral Agents; D009844:Oligosaccharides
keywords: Caliciviridae; Carbohydrate antigen; In silico screening; Influenza; Ro3; Scoring function