In silico pharmacological profiling of Ganoderma secondary metabolites to unravel the polypharmacological nature of Reishi

Abstract

The species complex around the so-called mushroom of immortality (Reishi), Ganoderma lucidum Karst. (Ganodermataceae), is known for a plethora of bioactive secondary metabolites, mainly lanostane-type triterpenes. This remarkable amount of structural information in combination with limited compound availability makes a rationalization of the individual Ganoderma constituents to biological actions on a molecular level extremely challenging. Taking these issues into account, a database was generated containing 279 chemical structures of so far known Ganoderma constituents. This was followed by subjecting this 3D multi-conformational molecular dataset to in silico parallel screening against an in-house collection of validated structure- and ligand-based pharmacophore models [1]. Influenced by traditional application fields of Ganoderma sp. the selection focused on representative druggable targets in the field of viral infections (5) and diseases related to the metabolic syndrome (22). In sum, 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 the hit targets or for the associated biological activity. By disclosing putative ligand-target interactions this study guided us towards assaying for inhibition of the influenza virus and human rhinovirus (e.g. see Fig.), and further serves as a basis to access yet undiscovered biological actions of Ganoderma secondary metabolites on a molecular level.