The Computational-Aided Drug Design technologies applied during Phase 1 of the project, led to fast virtual identification of known drugs (repurposing). Raloxifene’s clinical trial with 150 patients in 3 EU countries, has been completed, and the other 3 molecules were selected as clinical candidates. Also, the experimental test activities led to the development of 12 biological assays and to the test of 70000 molecules (+50000 and 20000 within E4C and COVIRAL project rspectively) of which 600 were found to be active.
Thanks to in silico technologies such as molecular dynamics simulations, we deployed precious web platforms to support the global research community with bioinformatics and simulation tools. The most complete (> 60 simulations) and the most informative (> 10 µs) set of SARS-COV-2 molecular dynamics simulations were released thanks to the best European HPC resources. In particular, in the initial phase of the pandemic, given the lack of experimental protein models, a web platform was created for the generation of homological models of viral proteins, useful for the entire scientific community (
https://swissmodel.expasy.org/(se abrirá en una nueva ventana)). This allowed the entire scientific community to get access to these outstanding data.
Then, the collaboration between the project Partners and the entities belonging to the Exscalate4CoV’s League, more than 35 viral proteins have been identified and experimentally solved, using X-ray techniques, allowing us to include high-quality structural information into our computational studies.
In November 2020, the beginning of Phase 2 was preceded by the largest virtual screening experiment ever carried out. This unprecedented simulation involved the two supercomputers of ENI and CINECA, and allowed to virtually test over 1 Trillion molecules against the most important viral proteins, in just 60 hours. This result confirms the real possibility of exploiting HPC platforms in cases of pandemics.
The impressive amount of data produced from the simulation was processed in collaboration with SAS, using artificial intelligence techniques and advanced analytics. Results are available on the portal 1trilliondock.exscalate4cov.eu and then on the portal mediate.exscalate4cov.eu co-designed with SAS to allow scientists around the world to carry out their own molecular docking simulations, benefiting from "state of the art" knowledge supplied by E4C project through the MEDIATE initiative.
To date, this initiative (MEDIATE - MolEcular DockIng AT home) - will give 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.
Experimental and theoretical data produced within the project led to the publication of 38 peer review papers with a global impact factor > 200 points 18 patents, underlining the high quality of the results produced till now. Other scientific works are in preparation and some of them were already submitted or are in the revision phase.
