PRACE, the Partnership for Advanced Computing in Europe, has issued an additional 10 awards of supercomputing resources, with a total of 227.6 million core hours for the European Union’s effort to combat COVID-19. This follows the first 10 awards recently announced by the organization.
Here’s a summary of the latest PRACE awards:
Led by Prof. Iñaki Tuñón from the University of Valencia, Spain, a research team has been granted 23 million core hours on the main partition of the MareNostrum4 system hosted by the Barcelona Supercomputing Center, Spain, as well as 288 000 core hours on its P9/V100 partition.
The group is conducting a computational study of the reactivity in the main protease – an enzyme that breaks down proteins and peptides – of SARS-CoV-2 to guide design of inhibitors. The team will analyze the binding of the substrate and the reaction mechanisms of the protease the COVID-19 virus. “The main protease (3CLpro) is an enzyme with essential role during the replication of the virus and is therefore an attractive drug target,” PRACE reported.
Compute resources from the Marconi100 system at Italy’s largest computing center, CINECA, have been awarded for a project led by Dr. Sonsoles Martin-Santamaria of the Spanish Research Council (CIB-CSIC) working on identification of inhibitors of SARS-CoV-2 S protein. Granted 25 million core hours on the system, the goal is to block the binding of virus spike S to the human cell receptor ACE2, stopping the virus from infecting the cell.
The scientists will use the generic drug library in the hope of repurposing an existing drug for “inhibitory activity” to block the coronavirus, possibly enabling a faster way through clinical trials.
Thirty-five million core hours on the Piz Daint system hosted by CSCS, the Swiss National Supercomputing Centre, has been awarded to Dr. Himanshu Khandelia from the University of Southern Denmark, who, with his team, will conduct molecular dynamics simulations and Markov State Models to study blocking viral entry into the human cells.
Entry happens through an ectodomain of the trimeric S protein of the coronavirus. The project concentrates on the “conformational transitions” in the S protein that make this binding possible, and may point to new drug targets.
PRACE awarded 16 million core hours on the Joliot-Curie Rome system hosted at GENCI, the French supercomputing facility, to Prof. Evangelos Daskalakis of the Cyprus University of Technology to study “epitope vaccines” based on the dynamics of mutated SARS-CoV-2 proteins.
The working hypothesis of Daskalakis’ team is to focus on proteins with lower mutation rates, which could be potential drug targets – or sources of epitopes, the part of an antigen that are recognized by the immune system, specifically by antibodies, B-cells, or T-cells.
Also at GENCI, with 40 million core hours on the Joliot-Curie KNL machine, Dr. Juan Torras of the Polytechnic University of Catalonia, Spain, is leading a team conducting a computational study to guide development of new SARS-CoV-2 detection “hyper-spectral platforms.” The project focuses on early and fast detection of the coronavirus in patients as well as its infection mechanisms, which could lead to new therapeutics and diagnostics based on antibodies.
The team will study silica and gold substrates with different antibodies with classical molecular dynamics. It will use a nanoparticle detector for comparative study among different antibodies, their orientation, and their interaction with silica and gold surfaces. The group also is working on interactions between antibodies virus spike of the HIV-1 to create novel immunosensor devices.
Forty-four million core hours on the Marconi100 system at CINECA has been awarded to Dr. Alfonso Gautieri from the Polytechnic University, Milan, to study blocking the SARS-CoV-2 spike protein through computer aided design of peptide inhibitors, which are chains of amino acids linked by peptide bonds.
The SPIKE-CAP project aims to design antiviral peptides with ultra-high affinity for the coronavirus spike protein (S) — and thus outcompete binding with human ACE2 and preventing infection — by using high-throughput computational deep scanning mutagenesis. The most promising candidate will be tested by a partner lab at Massachusetts Institute of Technology.
The Marconi100 at CINECA also will support a project led by Prof. Matteo Ceccarelli from the University of Cagliari, Italy targeting the Lysosome-Endosome system to avoid virus entry/exit in cells. Ceccarelli and his team have been awarded 7.9 million core hours on Marconi100 that PRACE said has “a chance for breakthroughs not only in the battle against the COVID-19, but also for other diseases like cancer and Parkinson.”
The project is based on the investigation of an unexplored key target: the lysosomal-endosomal TPC2 ion channels of the two-pore channel family, a system involved in the trafficking of cells. In 2015 it was proven how inhibiting TPC channels could stop Ebola and MERS-CoV. The team has been investigating the channels using molecular dynamics and metadynamics simulations.
Dr. Simone Melchionna from the National Research Council (CNR), Italy, and his team have been granted 30 million core hours on Hawk, hosted by Gauss Centre for Supercomputing (GCS) in Germany for “prognostic judgement of patient management based on the joint usage of pulmonary reconstruction, biomechanical simulations, physiological modelling, machine learning and AI.”
It’s hoped the supercomputer will generate predictive values for oxygen and carbon dioxide levels in different ventilation scenarios, based on acquired time series, operating conditions, postures, age, habits and other factors. The project is a collaboration between academic researchers, AI experts, a private entity and doctors from radiology and intensive care units (ICU).
Prof. Francesco Luigi Gervasio of University College London is leading a project awarded 6 million core hours on the Hawk machine at GCS for development of drugs interfering with the host translational inhibitor non-structural protein 1 (nsp1) of COVID-19.
Gervasio’s team is focused on fast mutation rate of the virus as a cause of resistance to antiviral drugs, requiring a combined therapy targeting different viral genes. The scientists will target the relatively less studied nsp1, which has 86 percent identity with SARS-CoV and has been determined as a major virulence factor. The aim is to explore the “druggability” of nsp 1 in search of therapeutics.
Finally, Prof. Maria João Ramos from the University of Porto, Portugal, has been awarded 370,000 node hours on the Piz Daint system at Switzerland’s CSCS for a drug discovery project aimed at blocking COVID-19’s main protease, preventing the virus from replicating.
The team will test commercial compound libraries with millions of compounds along with their in-house library. The goal is to identify chemical entities that can bind to a selected protein target.
