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Exscalate4CoV (E4C) is the public-private consortium backed by the European Commission’s H2020 program. It currently represents the most advanced center of competence aimed at fighting the coronavirus by combining the best supercomputing resources and artificial intelligence with state of the art experimental facilities up through clinical validation.
Advanced CADD, in combination with the high throughput biochemical and phenotypic screening [1-3], allowed the rapid evaluation of the simulation results and the reduction of time for the discovery of new drugs.
This approach is especially useful against pandemic viruses and other pathogens, where the immediate identification of effective treatments is of paramount importance.
High throughput biochemical and phenotypic screening enables scientists to test thousands of samples simultaneously. Using automation, the effects of thousands of compounds can be evaluated on cultured cells, or using biochemical in vitro assays. The goal of HTS is to be able to identify or “hit” compounds that match certain properties.
Through the EXSCALATE platform and the virtual screening protocols, E4C reached two outstanding milestone:
(1) selected the most promising drugs against coronavirus taken from the commercialized and developing drugs safe for humans. In particular on October 27, 2020 AIFA authorized the clinical study at IRCSS Lazzaro Spallanzani in Rome and IRCSS Humanitas in Milan to evaluate raloxifene (first molecule selected by Exscalate4CoV) as a potential treatment for covid paucisymptomatic patients who are in hospital or at home;
(2) on November 21 Exscalate4Cov performs in Italy the most complex supercomputing experiment to identify new therapies against Sars-Cov-2 virus. More than 70 billion molecules will be 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 will be 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.
The data generated so far have led to the creation of more than 28 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 https://www.exscalate4cov.eu/contribute.html#papers.
References:
1. Manelfi et al. 2021; https://doi.org/10.3390/molecules26040797
2. Kuzikov et al. 2021; https://doi.org/10.1021/acsptsci.0c00216
3. Gossen et al. 2021; https://doi.org/10.1021/acsptsci.0c00215
Speaker: Carmine Talarico achieves the degree in Pharmacy and a PhD in Pharmaceutical Sciences at the Magna Graecia University of Catanzaro. In 2018, he received the Award of excellence Paul Ehrlich MedChem Euro-PhD Network, refers to PhD Thesis with the title “Evaluation and Application of Molecular Modeling Algorithms to relevant Pharmaceutical Targets”. At the moment he works as a computational chemist at Dompé Farmaceutici SpA and is the leader of the computational Task in Exscalate4CoV project. He is also Project Leader of the PRACE granted project called Antarex for Zika, a project that has been recognized as having a clear societal impact that will harness the power of HPC to fight diseases that overwhelmingly affect developing countries. He is an expert in molecular modelling techniques such as structure/ligand-based drug design, molecular dynamics and docking simulation, and author and co-author of more than 20 works published on scientific journals.