Nobel Prize Arieh Warshel among authors of MEDIATE’s results published in Expert Opinion on Drug Discovery

Collaborative computing has attracted great interest because of the possibility of leveraging the efforts of researchers around the world. When the world was in the grip of Covid-19 in 2020, with various blockages around the world, through its Exscalate platfom Dompé brought together a consortium of partners to help fight it. This public-private consortium-Exscalate4Cov (E4C)-comprised of 18 institutions and research centers across Europe and supported by the European Commission's Horizon 2020 program-worked together to rapidly address the growing threat of COVID-19, which had spread worldwide as of December 2019.

Among the initiatives launched by the E4C consortium, the MEDIATE project was born with the goal of gathering a chemical library of NEW INHIBITORS OF SARS-COV-2 targeting the most relevant viral proteins, combining as much as possible VIRTUAL SCREENING SIMULATIONS and AI PREDICTIONS generated by the BEST researchers around the world.

This made it possible to benefit from the widespread worldwide experience of research groups involved in virtual screening studies to discover an optimized set of potential SARS-CoV-2 inhibitors to be tested and shared with the scientific community within a reasonable time frame. In this more general context, the choice of shared protein structures on which to focus simulations played a key role. Even today, this is still being pursued by inviting all interested researchers to contribute their simulations, on the basis of which improved and cross-referenced predictive models and consensus strategies can be developed.

The paper published in the prestigious scientific journal Expert Opinion on Drug Discovery - Dompé's first publication in co-authorship with a Nobel Laureate, Arieh Warshel and presents goals and results achieved by the Mediate project. A total of 32 users from 8 different countries participated; to date 114,418 total predictions and 22,309 docked molecules have been generated. 

Paper Highlights 

The contributions (docking results) submitted to MEDIATE will be used to develop global consensus models with artificial intelligence techniques, and the most promising compounds will be tested experimentally.

The compounds with the best scores, selected from the valuable molecular docking simulations provided by project participants, are tested by us in BIOCHEMICAL and CELL SCREENING to assess their real efficacy.

Finally, a reference table shows some of the molecules with the highest scores, selected for the best polypharmacological profile, that have been experimentally validated or are in clinical trials for COVID-19. Reported for each pocket are normalized scores above the corresponding mean values plus twice the standard deviation, a well-known statistical criterion used here as a threshold for identifying potentially active molecules.

While targeting COVID-19, MEDIATE can represent a prototype collaborative platform for running standardized virtual screening campaigns by sharing the necessary input structures.