Hippo(crates): An integrated atlas for natural product exploration through a state‑of‑the art pipeline in chemoinformatics

Abstract

. Modern drug discovery and pharmaceutics benefit from nature. Natural products (NPs) are used as a source of therapeutic agents with beneficial uses. Currently, there is considerable interest in the exploration of NPs for drug discovery and continuous investigations on the therapeutic claims and mechanisms of herbal medicines. To date, approxi‑ mately one million NPs have been isolated and subjected to experimental assays to evaluate quantitative biological activities. This renders the use of an integrated database to assemble and correlate this valuable information from the literature, experimental studies and databases necessary. Although databases contain a large volume of information, it is frequently difficult and complex, even in well‑organized databases, to extract the required information. Novel databases must be accompanied by efficient algorithms and techniques in order to extract beneficial knowledge by a simple query. The Hippo(crates) database aims to fill this gap in the field of chemoinformatics and natural products by providing retrieval not only linked to the Hippo(crates) database, but also to other worldwide chemical and biological databases. Part of the OPENSCREEN‑GR project, the Hippo(crates) Database Graphical User Interface (HDGUI) web server was developed to provide a user‑friendly access interface, integrating anno‑ tated information of NP origin (sources and species), biological activities, physicochemical properties, linear and 3D chemical structure, as well as relative terms that correlate chemical compounds and their use. In its current version (V1.0), the Hippo database provides 45,300 NPs, NP derivatives and synthetic compounds, which are separated into 32 major categories, including biological or medicinal properties. In the database, 22,830 NP source organisms are correlated, with >100,000 terms, including biological pathways, target organisms, target diseases, target types, target proteins and pathogens, and 6,070 three‑dimensional structures of NP target proteins. For each entry, a cluster with similar compounds and a ligand‑based or structure‑based pharmacophore model is provided. The portal is designed as an easy‑to‑use web tool where the user can easily search, extract and correlate informa‑ tion and data for natural product chemical compounds through various fields, such as categories, keywords, targets, species, or two‑dimensional or three‑dimensional similarity structure in the Hippo(crates) atlas of the NP database.