February 17, 2020

Exscalate4CoV: EU’s supercomputing and life science champions gear-up to fight Coronavirus pandemic

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  • 18 EU top organizations from 7 countries bid for Horizon 2020 tender against 2019-nCoV
  • Exscalate, world’s most performing intelligent supercomputing platform (3 million molecules processed per second, 500 billion molecules library)
  • Aim: immediate identification of molecules effective against Coronavirus and new tools against future pandemics

Milan 17 feb. 2020 - Italy is leading Exscalate4CoV (E4C), the public-private consortium bidding for the European Commission’s Horizon 2020 tender for projects to counter the Coronavirus pandemic and improve the management and care of patients.

E4C aims at leveraging EU’s supercomputing resources coupling them with some of the continent’s best life-science research labs to counter international pandemics faster and more efficiently.

At the core of the project is Exscalate (EXaSCale smArt pLatform Against paThogEns), at present the most powerful (and cost-efficient) intelligent supercomputing platform in the world, developed by Dompé. Exscalate (exscalate.eu) leverages a "chemical library" of 500 billion molecules, thanks to a processing capacity of more than 3 million molecules per second.

The E4C consortium, coordinated by Dompé farmaceutici, is composed by 18 institutions form seven European countries: Politecnico di Milano (Dept. of Electronics, Information and Bioengineering), Consorzio Interuniversitario CINECA (Supercomputing Innovation and Applications), Università degli Studi di Milano (Pharmaceutical science Department), Katholieke Universiteit Leuven, International Institute Of Molecular And Cell Biology In Warsaw (LIMCB), Elettra Sincrotrone Trieste, Fraunhofer Institute for Molecular Biology and Applied Ecology, Bsc 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 BigData, Istituto Nazionale di Fisica Nucleare (INFN), Istituto nazionale per le malattie infettive Lazzaro Spallanzani and Chelonia Applied Science.

The aim of E4C is twofold, identify molecules capable of targeting the coronavirus (2019-nCoV) and develop a tool effective for countering future pandemics to be consolidated over time. More specifically E4C aims to:

  • Establish a sustainable example for a rapid scientific answer to any future pandemic scenario. The model leverages a rapid and effective High Performance Computing platform for the generation and analysis of3D models and experimental 3D structure X-ray resolution of protein targets from pandemic pathogens
  • Drive a fast virtual identification of known drugs (repurposing) or proprietary/commercial candidate molecules to be further experimentally characterized
  • Define a workflow scheme for biochemical and cellular screening test to validate the candidate molecules in previous points and assure, through phenotypic and genomic assays.
  • Prepare together with EMA a development plan for successful candidates for direct “first in human” kind of studies or for further testing in animals for bridging studies.
  • Identification of 2019-nCoV genomic regions involved in host adaptation, pathogenicity and mutations.

E4C will have two highly interconnected workstreams of activities. One will be primarily computerized and will rely on bioinformatic and chemoinformatic technologies and algorithms, while the second will be focused on a genomic, biochemical and biological approach. Starting from known bioinformatic information on protein targets, 3D molecule structures needed to exploit EXSCALATE platform potential will be prepared. This activity has already started.

The supercomputing component of the project will be then exploited to model future mutations of the virus. These activities will allow to identify candidate molecules (either from repurposing libraries or from proprietary or commercial compound libraries) which will then be provided and/or synthetized to be tested. In parallel, E4C partners shall start the protein production for some of the identified sequences.

The consortium will also open the Exscalate platform to external partners willing to cooperate in the drug hunting exercise, as previously with the Zika virus. This considerable effort to test roughly more than 25,000 compounds will ensure E4C doesn’t lose any active candidate molecules and will evaluate other possible mechanisms previously underestimated. The project will also use inverse genomic screening to identify host factors associated with virus infection and connectivity mapping analysis to predict relevant host-specific compounds for testing.

The further, development of a specific Coronavirus animal model to test the outcome of the E4C will help researchers bridge from the selection of active compounds to a possible fast first dose in humans, following EMEA directives and managed by Spallanzani Hospital Partner.

Finally, researchers will work to make the Exscalate platform a sustainable resource for an emergency engine for compound identification to be deployed in all future pandemic emergencies.

1 This performance exceeds by far the current "state of the art" technology which is also the subject of a recent article in Nature - 6 February 2019, (https://www.nature.com/articles/s41586-019-0917-9) whereby a "chemical library" of 138 million molecules of a single target has been reached, with a processing capacity of less than 2 thousand molecules per second.

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