Tag: Supercomputing, VirtualScreening, HPC, health, COVID-19
Researchers: Cristina Silvano, Gianluca Palermo
Department: DEIB – Department of Electronics, Information and Bioengineering
A drug has been found which is able to counter the SARS-CoV-2 virus, responsible for COVID-19. The drug in question is Raxilofene and it has been identified thanks to the European Exscalate4CoV project, supported by the European Horizon 2020 project for research and innovation, with the collaboration of Politecnico di Milano, Dompé Farmaceutici, Cineca and another 15 partners throughout Europe.
Exscalate4CoV uses the fastest pharmaceutical research platform in the world, created with the collaboration of professors Gianluca Palermo and Cristina Silvano from the Department of Electronics, Information and Bioengineering of Politecnico di Milano. From an archive of about 500 billion molecules, the EXSCALATE platform (EXaSCale smArt pLatform Against paThogEns) is able to select the molecules that meet certain compatibility requirements with the SARS-CoV-2 virus. Thanks to the CINECA supercomputers, researchers have analyzed over 10 million pharmaceutical molecules, identifying in Raxilofene the most promising molecule to inhibit the replication of coronavirus inside human cells. In vitro tests have confirmed the results processed by the platform. Raxilofene has been used for years against osteoporosis and is well-tolerated by the human body: this will make it possible to rapidly move forwards to the clinical test phase on patients affected by COVID-19. “One of the most computationally complex phases was the 3D modeling of the virus proteins, which was unknown until just a few months ago” comments Palermo. “Now we have a good model and the Exscalate platform is able to compare it with over 500 billion molecules in just a few weeks, identifying the molecules able to inhibit the virus from replicating”. With the start of the clinical study, the first phase of the project can now be considered over. Since the approval process to test the drug on people has been completed, the IRCSS Lazzaro Spallanzani in Rome and IRCSS Humanitas in Milan research hospitals have been carrying out trials on 450 patients since the end of October. During the second phase of the project, almost 500 billion molecules will be analyzed, many of these have never been used and are not present in nature. While the wait for the results continues, if one of these compounds proves to be interesting, moving forwards to the clinical phase will take time: tests to verify whether a molecule is toxic for humans can take between 5 and 10 years. This is why the project has prioritized the analysis of drugs already being used for other pathologies.
At the time of writing, researchers are carrying out the largest virtual molecule screening experiment in the world. The Politecnico di Milano team is at the forefront of this experiment, which will be developed using the two most powerful supercomputers in Europe: the ENI HPC5 and the CINECA Marconi-100 system. 70 billion molecules evaluated on 15 active sites of 12 SARS-CoV-2 proteins for a total of over one thousand billion evaluations. This number goes well beyond the “just” 2 billion evaluations carried out at the Oak Ridge National Lab in the United States on a single protein for the same reason, using the second most powerful supercomputer in the world, and the billion evaluations made by the same DOMPE-POLIMI-CINECA work group against the Zika virus, which at the time were considered unique experiments. “The EXSCALATE platform has the peculiar characteristic of being designed from the outset for situations like the one we are living through at the moment, where urgent calculations must be deployed at speeds that only supercomputers can achieve. At the moment, we are carrying out an experiment in only a few days which as little time ago as last year, would have taken tens of months” comments Palermo.
The project is coordinated by Dompè Farmaceutici alongside a multidisciplinary team and aims to continue to collaborate with Politecnico di Milano and CINECA during every phase to develop the EXSCALATE platform, thus accelerating the computational process in the search for new drugs and maximizing the efficiency of the new generation of supercomputers. “However, we are currently directly involved with just the computational challenge which we are really excited about thanks to its uniqueness, but no less important will be the next phase when the research carried out will be more than just an end in itself. The data produced by the simulation will be analyzed by Dompé Farmaceutici to identify interesting molecules that may be active on numerous proteins, and will also be made available to the scientific community”. Thanks to the recent investment decided by Italy and Europe, in October it was announced that a new supercomputer called Leonardo will be installed at CINECA next year, which should reach 250 thousand billion calculations per second (petaflop), 10 times more than the current rate. The Politecnico di Milano team is already geared up for this new challenge, also thanks to a new European project called LIGATE (LIgand Generator AT Exsascale), which will see the DOMPE – POLIMI – CINECA team working together for a further 3 years.
