PRACE is joining the battle against COVID-19 by providing huge computational power – 195 Million core hours – to the first ten projects awarded under the Fast Track Call for Proposals to support the mitigation of the impact of the pandemic.
There are currently no registered therapies for treating coronavirus infections. Because of the time-consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases.
The studies awarded by PRACE independently analyzed a number of proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures and built 19 structures that could analyzed via homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries, including ZINC drug database and a database of natural products.
Some of the projects made the structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) visible. In addition, a database of 78 commonly used anti-viral drugs, including those currently on the market and undergoing clinical trials for SARS-CoV-2, was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted.
These projects will provide new lead compounds and targets for further in vitro and in vivo studies of SARS-CoV-2 (virus strain causing coronavirus disease COVID-19), new insights for those drugs currently undergoing clinical studies and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.
All this is possible thanks to one of the most powerful tools for finding possible medicines and inhibitors: virtual ligand screening and virtual drug design. Both techniques directly use supercomputer simulations, extreme-scale supercomputing simulations, that can only be performed on supercomputers with tens of thousands of cores. PRACE provides just such supercomputers to the research community.
With these powerful machines, the first 10 “HPCvsVirus” projects will be realized.
Project Summaries:
- COVID-HP
- Characterisation of a peptide network with a combined anti-viral and anti-inflammatory activity against COVID-19
- COVID19: Computational screening and improvement of viral protein inhibitors
- Characterization of SARS-CoV-2 envelope small membrane protein (E)
- Polypharmacology-based anti-viral design
- Drug design on the 3CL-pro (Mpro) target protein of SARS-CoV2 using fast switching massively parallel alchemical approaches for absolute binding free energy determination
- Molecular Dynamics investigation of the interaction between ACE2 and the spike glycoprotein of SARS-CoV-2, in comparison with its predecessors from bat and pangolin
- CardioVascular-COVID
- Targeting the interface of the COVID-19 spike protein with the ACE2 receptor
- Targeting conformational changes implicated in early events of viral entry
