Correct annotation of data is a crucial factor defining the quality of analysis and predictions in chemoinformatics. In the field of antiviral activity data, we have developed a scheme for taxonomy annotation of ChEMBL assays, which allowed us to create the ViralChEMBL database. In this database all data points are linked to the taxa defined by the International Committee for Taxonomy of Viruses (ICTV), and antiviral activity profiles are available for more than 250,000 compounds, comprising more than 600,000 data points. In this presentation we describe the new version of ViralChEMBL, incorporating the latest ChEMBL data and the latest version of ICTV taxonomy. We also show several use cases, where chemical space maps and graphs are employed to depict and mine information contained in ViralChEMBL. Generative Topographic Mapping (GTM) is a well-known approach to dimensionality reduction and chemical space visualization. Universal GTMs (trained in order to maximize their proficiency to predict a vast panel of unrelated biological properties) were previously suggested as a useful tool for intuitive analysis of structure-property relations in chemical space. One of the advantages of the GTM approach is the ability to calculate responsibility patterns (RPs), defining compounds by their probabilities to reside on particular nodes. We applied the universal maps for the analysis of ViralChEMBL data and for the prediction of new antiviral compounds. Thus, the similarity between structures can be visualized and GTM can be used as a tool for compound repurposing. DrugBank and an in-house database were placed on the maps, to identify compounds that could be repurposed as antivirals because they reside in areas with high populations of validated antivirals. Structures sharing the same RPs were retrieved and manually analysed. The use of consensus RPs (RPs from more than one map) allowed filtering out pairs of unrelated compounds, accidentally sharing a common location with respect to a single map. Several compounds were selected for further experimental antiviral activity evaluation against the representatives of Flavivirus and Enterovirus genera.

Mapping of antiviral chemical space with ViralChEMBL: Use cases and new findings

255th National Meeting (2018)

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