title: Structure-based virtual screening for the discovery of natural inhibitors for human rhinovirus coat protein.
abstract: Inhibitors of the human rhinovirus (HRV) coat protein are promising candidates to treat and prevent a number of upper respiratory diseases. The aim of this study was to find antiviral compounds from nature, focusing on the HRV coat protein. Through computational structure-based screening of an in-house 3D database containing 9676 individual plant metabolites from ancient herbal medicines, combined with knowledge from traditional use, we selected sesquiterpene coumarins from the gum resin asafetida as promising natural products. Chromatographic separation steps resulted in the isolation of microlobidene (1), farnesiferol C (2), farnesiferol B (3), and kellerin (4). Determination of the inhibition of the HRV-induced cytopathic effect for serotypes 1A, 2, 14, and 16 revealed a dose-dependent and selective antirhinoviral activity against serotype 2 for asafetida (IC50 = 11.0 microg/mL) and its virtually predicted constituents 2 (IC50 = 2.5 microM) and 3 (IC50 = 2.6 microM). Modeling studies helped to rationalize the retrieved results.
authors.affiliation: Institute of Pharmacy/Pharmacognosy, University of Innsbruck, Innrain 52, A-6020 Innsbruck, Austria. judith.rollinger@uibk.ac.at
authors.forename: Judith M
authors.initials: JM
authors.lastname: Rollinger
authors.forename: Theodora M
authors.initials: TM
authors.lastname: Steindl
authors.forename: Daniela
authors.initials: D
authors.lastname: Schuster
authors.forename: Johannes
authors.initials: J
authors.lastname: Kirchmair
authors.forename: Kathrin
authors.initials: K
authors.lastname: Anrain
authors.forename: Ernst P
authors.initials: EP
authors.lastname: Ellmerer
authors.forename: Thierry
authors.initials: T
authors.lastname: Langer
authors.forename: Hermann
authors.initials: H
authors.lastname: Stuppner
authors.forename: Peter
authors.initials: P
authors.lastname: Wutzler
authors.forename: Michaela
authors.initials: M
authors.lastname: Schmidtke
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D036022:Capsid Proteins / Q000037:antagonists & inhibitors*; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D005309:Ferula / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D028321:Plant Preparations / Q000494:pharmacology; D012229:Rhinovirus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014468:Umbelliferones / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D010948:Viral Plaque Assay
chemical_list: D000998:Antiviral Agents; D036022:Capsid Proteins; D028321:Plant Preparations; D012717:Sesquiterpenes; D014468:Umbelliferones