Nutraceutical search through the pipeline of pharmacophore-based virtual screening

Nutraceuticals are food or their parts, present in conventional or non-conventional form, with verified safety and health benefits, beyond their nutritional value. In this work, we describe a novel pipeline for nutraceutical compounds research in the field of pharmacophore screening, providing a new idea for drug discovery. In the first step, to identify novel nutraceuticals potentially active as inhibitors of a given enzyme, a pharmacophore model is generated, with its key chemical features, starting from the experimental structure of the complex with known protein inhibitors, with pharmacophores ranking based on statistical values of sensitivity and specificity. After the validation step, this pharmacophore model is used for 3D structural screening and mapping against a subset of known nutraceutical compounds, generated through DrugBank or against special subsets from ZINC (ZINC Drug Database - Zdd and ZINC In Man - Zim). Moreover, molecular docking is performed to verify binding affinity of compounds. The hits with a good binding energy are then investigated in more details, compared with their pharmacophore features and analysed for their interacting residues. Then, to have an in silico interpretation of the potential activity of the compounds, an integrated investigation is performed, by mining literature reports about the effects of the specific compound (or food containing it) against human diseases, extracting expression data from omics repositories, in the view of integrating these information with molecular pathways and networks. Output of our pipeline are candidates for in vitro and in vivo experiments, to test the hypothesis and verify if they could become novel potential drugs.