title: Accessing biological actions of Ganoderma secondary metabolites by in silico profiling.
abstract: The species complex around the medicinal fungus Ganoderma lucidum Karst. (Ganodermataceae) is widely known in traditional medicines, as well as in modern applications such as functional food or nutraceuticals. A considerable number of publications reflects its abundance and variety in biological actions either provoked by primary metabolites, such as polysaccharides, or secondary metabolites, such as lanostane-type triterpenes. However, due to this remarkable amount of information, a rationalization of the individual Ganoderma constituents to biological actions on a molecular level is quite challenging. To overcome this issue, a database was generated containing meta-information, i.e., chemical structures and biological actions of hitherto identified Ganoderma constituents (279). This was followed by a computational approach subjecting this 3D multi-conformational molecular dataset to in silico parallel screening against an in-house collection of validated structure- and ligand-based 3D pharmacophore models. The predictive power of the evaluated in silico tools and hints from traditional application fields served as criteria for the model selection. Thus, the focus was laid on representative druggable targets in the field of viral infections (5) and diseases related to the metabolic syndrome (22). The results obtained from this in silico approach were compared to bioactivity data available from the literature. 89 and 197 Ganoderma compounds were predicted as ligands of at least one of the selected pharmacological targets in the antiviral and the metabolic syndrome screening, respectively. Among them only a minority of individual compounds (around 10%) has ever been investigated on these targets or for the associated biological activity. Accordingly, this study discloses putative ligand target interactions for a plethora of Ganoderma constituents in the empirically manifested field of viral diseases and metabolic syndrome which serve as a basis for future applications to access yet undiscovered biological actions of Ganoderma secondary metabolites on a molecular level.
authors.affiliation: Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria. Electronic address: ulrike.grienke@uibk.ac.at.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Grienke
authors.affiliation: Institute of Pharmacy/Pharmaceutical Chemistry, Computer-Aided Molecular Design Group, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
authors.forename: Teresa
authors.initials: T
authors.lastname: Kaserer
authors.affiliation: Institute of Pharmacy/Pharmaceutical Chemistry, Computer-Aided Molecular Design Group, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Pfluger
authors.affiliation: Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
authors.forename: Christina E
authors.initials: CE
authors.lastname: Mair
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Althanstraße 14, 1090 Vienna, Austria.
authors.forename: Thierry
authors.initials: T
authors.lastname: Langer
authors.affiliation: Institute of Pharmacy/Pharmaceutical Chemistry, Computer-Aided Molecular Design Group, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Schuster
authors.affiliation: Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria; Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna, Althanstraße 14, 1090 Vienna, Austria.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Rollinger
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015394:Molecular Structure; D011134:Polysaccharides / Q000494:pharmacology; D020940:Reishi / Q000737:chemistry*; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D004365:Drugs, Chinese Herbal; D011134:Polysaccharides; D014315:Triterpenes
keywords: Antiviral targets; Ganoderma lucidum; Ganodermataceae; Metabolic syndrome; Pharmacophore profiling; Triterpenes; Virtual screening