Exscalate4Cov: MEDIATE (MolEcular DockIng AT home)

CORONAVIRUS PANDEMIC:

Exscalate4Cov performs in Italy the most complex supercomputing experiment to identify new therapies against Sars Cov2 virus.

During the weekend of the 21st of November 2020, the public-private Consortium Exscalate4Cov, supported by the European Commission, carried out the most complex supercomputing simulation ever realized. The objective was to simulate the behavior of the Sars Cov 2 virus to identify the best therapeutic treatment.

More than 70 billion molecules were simulated on the 15 active interaction sites of the virus for a total of more than a thousand billion interactions evaluated in just 60 hours. This was possible thanks to the simultaneous availability of the computing power (81 petaflops: millions of billions of operations per second) of Eni's HPC5, the most powerful industrial supercomputer in the world, of CINECA's Marconi100, and the virtual screening software accelerated by the Politecnico di Milano and Cineca, and the Exscalate molecular library from Dompé.
Using this technologies/method, it has been possible to reach the new goal of 5 million simulated molecules per second, making the most out the Supercomputing infrastructure. As a comparison, the Italian simulation is more than 300 times bigger and 500 times faster than the one realized in the USA in June this year. (for more details: https://blogs.nvidia.com/blog/2020/05/26/covid-autodock-summit-ornl/)
The data from the simulation was processed with SAS Viya using artificial intelligence techniques and advanced analytics.  Results were available in real time on the portal 1trilliondock.exscalate4cov.eu and then on the portal mediate.exscalate4cov.eu, designed in collaboration with SAS to allow scientists around the world to carry out their own simulations, benefiting from "state of the art" knowledge.

Research groups around the world can use virus protein models and chemical libraries to generate new predictions using different approaches of artificial intelligence and molecular mechanics simulations.
The consortium will make available 10 million dedicated computing hours and the necessary technological infrastructure. MEDIATE - MolEcular DockIng AT home -  gives free access to the largest database available today on the Sars-CoV-2 Virus both from a structural (three-dimensional structures) and functional (proteins interacting with human cells) point of view, including all the molecular dynamics involved in cellular interaction and active sites for potential drug entry.
In this regard, the molecular bank of MEDIATE has been generated considering the main classes of molecules, which have been selected to allow an accelerated clinical development. The library contains: 10 thousand drugs, 400 thousand natural products, 70 thousand nutraceuticals, 100 million oligopeptides, 5 million molecules already on the market for research purposes, and 72 billion de novo molecules easily synthesized.
The MEDIATE portal collects the predictions made by research groups around the world (crowdsourcing) combining them into a single model using the neural networks and artificial intelligence from SAS with the aim of identifying new and more effective treatments against COVID-19, in the shortest possible time.

The MEDIATE project can rely on a scientific board (coordinated by the project partner Chelonia Applied Science) of the highest level: Nobel Prize for Computational Chemistry Prof. Arieh Warshel, Rossen Apostolov Executive Director of BioExcel, European Centre of Excellence for Biomolecular Computational Research, Igor Tetko of Helmholtz Zentrum München and Prof. Yang Ye of Shanghai Institute of Materia Medica.
Phase 1 of the EXSCALATE4COV project - with a screening carried out on 400 thousand molecules (safe-in-man drugs and natural products) and a specific test to evaluate 9000 promising molecules - ended with the identification of one molecule - raloxifene – now under a phase III clinical trial project submitted and approved by AIFA. The patent file was filed on May 6, 2020 by Dompé farmaceutici, Fraunhofer Institute at the University of Leuven in order to promote universal access to the treatments that may result, as defined by the guidelines of the consortium itself.
The data generated so far have led to the creation of 12 peer reviewed articles and evidence from over 20 thousand in vitro experiments. The international magazine "International Journal of Molecular Sciences" has dedicated a special issue to the project EXSCALATE4COV (https://www.mdpi.com/journal/ijms/special_issues/Exscalate4CoV), you can find the scientific production of the consortium on the website.

The Exscalate4Cov (www.exscalate4cov.eu) consortium, supported by the the EU’s Horizon 2020 programme for research and innovation, is coordinated by Dompé farmaceutici, and composed by 18 member institutions from seven European countries: Politecnico di Milano (Dept. of Electronics, Information and Bioengineering), Consorzio Interuniversitario CINECA (Supercomputing Innovation and Applications), Università degli Studi di Milano (Department of Pharmaceutical Sciences), International Institute of Molecular and Cell Biology in Warsaw (Warsaw, Poland), KU Leuven, Elettra Sincrotrone Trieste, Fraunhofer Institute for Molecular Biology and Applied Ecology, BSC Barcelona Supercomputing Centre, Forschungszentrum Jülich, Università Federico II di Napoli, Università degli Studi di Cagliari, SIB Swiss Institute of Bioinformatics, KTH Royal Institute of Technology (Department of Applied Physics), Associazione Big Data, Istituto Nazionale di Fisica Nucleare (INFN), Istituto nazionale per le malattie infettive Lazzaro Spallanzani and Chelonia Applied Science.-https://www.exscalate4cov.eu/consortium.html League: ENI, SAS, Alfasigma, CFEL Center for Free-Electron Laser Science, MMV Medicines for Malaria Ventures, Esteve Pharmaceutical, University of Basel Biozentrum, University of Basel Innovation Office, University of Basel Department of Pharmaceutical Sciences, D-wave, Pierre fabre, Greenpharma, University of Sheffield - Sheffield Institute for Translational Neuroscience – SITraN, Dassault Systemes- Biovia, Institute of Food Science Research, CECAM Centre Européen de Calcul Atomique et Moleculaire, Nanome, Esteco, IT4Innovation, Università degli Studi della Tuscia, Sofia University “St. Kl. Ohridski”, Faculty of Physics, Institut Cochin- https://www.exscalate4cov.eu/league.html