Demonstrator 1: European Open Science Cloud resources for Chemical Biology and Structure-Based Drug Discovery workflows
A huge amount of data is produced daily from drug sensitivity screens or protein/ligands 3D structural interaction screens. However, from this data produced, only a very small subset of datasets are published and made publicly available. The majority of data produced is lost due to lack of annotation/standardisation that would make the data FAIR and re-usable for all. Furthermore, structural data and bioactivity data are so far not interconnected and can not be easily integrated.
In this Demonstrator project, scientists from different research infrastructures (Instruct-ERIC, EU-OPENSCREEN, EATRIS, ELIXIR, EU-EBI ) collaborated to develop a set of tools to increase the FAIRness of chemical biology data and structural data and to enable the integration of structural biology data and chemical biology data to increase access and re-use of resources.
The fragalysis platform was developed enabling rapid access to data from fragment screens in a collaborative environment. Fragalysis is a ligand centric platform that provides information regarding ligands and their target. Virtual screening workflows were developed alongside Galaxy that also allow to rapidly screen follow-up compounds for Mpro hits. (More info:https://covid19.galaxyproject.org/cheminformatics). The development of Fragalysis with EOSC-Life allowed the platform to have impact in COVID-19 work for instance by allowing almost real-time release of initial fragment screen via Fragalysis to the worldwide community.
EU-OPENSCREEN is working on the development of The ECBD (the European Chemical Biology Database) that will be the central repository for Chemical Biology data generated within the EU-OS network. The aim with this repository is not make these chemical biology resources more FAIR by making the data more accessible, establish standard formats and identifiers for molecules and targets, establish standards for ontologies and vocabulary for the description of the process of results acquisition and finally make the description process user friendly for the data uploader. ECBD will be released in 2021 at ecbd.eu
Drug sensitivity screens are nowadays increasingly used for pre-clinical drug discovery and clinical trial optimisation A web portal called MICHA was created and is already in use to facilitate the annotation of critical drug sensitivity assay components and thus increase the FAIRness of drug sensitivity screening data.
Demonstrator 1 also actively contributed to the COVID-19 research by making SARS-CoV-2 data available in ChEMBL to compile a list of drugs that might be of interest in the current pandemic. To this purpose, datasets from different source were compiled in ChEMBL for deeper analysis.
When we came to EOSC-Life, what we had really was a prototype of an application with some ideas of how we might help our users to access and use fragment screening data but we didn’t really have a well-defined set of goals…in fact we might not have even known what we wanted to achieve. And what EOSC-Life’s really allowed us to do is to find what those goals are and achieve them.
— Rachael Skyner
Attending the workshop and hackathon was a great way to precipitate and catalyse discussions with the EOSC community and that led to the development of whole new approaches within Fragalysis which was extremely good… I think the general experience with EOSC-life, I’m biased as I’m leader of work package one, but it’s a unique opportunity to work across different scientific domains and different resource providers.
Identification of inhibitors of SARS-CoV-2 3CL-Pro enzymatic activity using a small molecule in-vitro repurposing screen
Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, Andrea Zaliani
bioRxiv 2020.12.16.422677; doi: https://doi.org/10.1101/2020.12.16.422677