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The ongoing COVID-19 pandemic is having a devastating effect on society. To overcome it, research communities must take coordinated actions and share efforts, expertise, and technologies. This is particularly important as Europe works towards developing potential treatments and vaccines for the disease.
“Both the public and private sectors are undertaking massive concerted efforts in tackling this crisis,” says Rossen Apostolov, BioExcel Executive Director. “Unquestionably, the discovery of a vaccine and cure will be of paramount importance for the long-term control of SARS-Cov-2’s spread, as well as related pathogens.”
As one of Europe’s leading centres for computational biomolecular research, BioExcel develops cutting-edge software applications and provides expert support in the areas of biomolecular integrative modelling, molecular dynamic simulations, free energy calculations, and docking. This unique expertise and suite of applications makes the centre well-positioned to quickly respond to a global pandemic.
When the COVID-19 crisis struck, BioExcel immediately launched a series of SARS-CoV-2 research initiatives. Specifically, numerous collaborations were established, user support was extended, and priority access to the centre’s supercomputing facilities was provided. “International collaboration is critical to addressing this grand challenge,” adds Apostolov. “If we want to succeed, we need to bring together the international research community.”
BioExcel is participating in numerous projects in support of COVID-19 research, and below we highlight a few.
Expanding understanding through simulations
HADDOCK, one of BioExcel’s core software applications, is an essential tool developed by Utrecht University and used by more than 17 000 researchers worldwide. It allows scientists to study the complex interactions between the virus and human proteins and predict how small molecules target the virus’ key proteins.
“These simulations are essential to our understanding of, for example, how to block the COVID-19 protease, the enzyme responsible for breaking down the expressed viral polypeptidic chain into functional units”, explains Alexandre Bonvin, the lead developer of HADDOCK.
Using the high throughput computing resources available via the European Open Science Cloud, the HADDOCK team screened over 2 000 accepted drugs against the SARS-CoV-2 protease in just three days. “Our hope is to identify potent inhibitors,” adds Bonvin. “The initial results have revealed interesting compounds, some of which are already in clinical trials, and thus supporting the validity of the screening method.”
RdRp as an ideal drug target
Before vaccines become available, antiviral drugs can be used to halt the viral replication, minimise health effects, and reduce the virus’ spread. Coronaviruses rely on a specific RNA-dependent RNA polymerase (RdRp), an enzyme that builds long chains of nucleic acids to replicate their viral RNA genome. Because humans lack such proteins, RdRp is an ideal drug target.
Unfortunately, as of now, only a handful of antiviral drugs have been developed against other coronaviruses, including Remdesivir, Faviripavir and EIDD-2801. Due to the nature of SARS-CoV-2, however, these drugs may not be effective. That’s why HADDOCK performed a second screening against RdRp. “Cocktails of approved drugs acting against multiple viral proteins might offer an attractive short-term solution for combating the virus while we wait for an effective vaccine,” says Bonvin.
The role of supercomputers
BioExcel is also developing and supporting some of the most popular tools that research groups are using to simulate proteins on supercomputers. “Supercomputers provide new possibilities for understanding how SARS-CoV-2 binds to and infects the cell, which helps us identify antiviral candidates that might prevent this process,” says Erik Lindahl, Scientific Director of BioExcel. “Our applications, such as GROMACS, allow us to use hundreds of thousands of computer processors simultaneously for extremely fast simulations of biological systems.”
For example, partners from the Max-Planck Institute, the Institute for Research in Biomedicine, and KTH Royal Institute of Technology are using supercomputer simulations to gain the missing structural insights needed to understand a drug’s mode of action, predict the effects of chemical modifications, and design better inhibitors.
“Only through coordinated efforts and strong collaborations between academia and industry will we be able to overcome pandemics such as COVID-19,” adds Lindahl. “Centres such as BioExcel play a vital role in facilitating this collaboration and building the expertise we need to succeed.” The work of the BioExcel project has since also been continuing in a follow-up project, BioExcel-2, which is due to run until December 2021.