The latest on finding a treatment for COVID-19
First, state-of-the-art supercomputers will analyze 500 billion chemical molecules. This will help scientists to select substances with potential therapeutic properties. Next, the experimental part of the project will be launched, with molecular biologists stepping into their labs. We asked Dr. Marcin Nowotny from the International Institute for Molecular and Cellular Biology in Warsaw to tell us more. His team is working on developing an effective therapy for the coronavirus SARS-CoV-2.
The project, financed by the EU, is named Exscalate4CoV. It is implemented by a public-private consortium led by the Italian biopharmaceutical company Dompé. The group includes 18 institutions from Italy, Switzerland, Belgium, Germany, Sweden, Spain and Poland. We are represented Dr. Marcin Nowotny’s team at the International Institute for Molecular and Cellular Biology.
Supercomputers searching for treatment
The core of the project is the Exscalate platform designed by Dompé. It uses a virtual chemical library comprising 500 billion molecules. “It is capable of conducting computational tests on over three million molecules per second. The idea is to find those which bind the viral proteins and inhibit them. Such substances are potential antiviral compounds,” says Dr. Nowotny.
Exscalate is the most powerful and cost-effective computer platform of its kind in the world. To make the most of its potential, it will be connected to the EU’s network of supercomputers. The activity of selected substances will then be tested through series of experiments.
The experimental part of the project
The next step is to gain an understanding of how the coronavirus SARS-CoV-2 binds potential therapeutic compounds. Scientists will define three-dimensional atomic structures of viral proteins with selected molecules. “This will help us to elucidate the mechanism of action of selected substances and to optimize their chemical structure to enhance their properties,” explains Dr. Nowotny.
“The idea is that the therapeutic molecule fits perfectly with the viral protein molecule. This means the two molecules are bound strongly together and the viral protein is effectively inhibited, a bit like a stake plunged into a complex mechanism. At the same time, it is important that our chosen molecule does not bind to any human proteins, because this could affect or inhibit their functioning and lead to toxic effects,” he continues.
His team, alongside colleagues from the Elettra synchrotron in Italy, is responsible for defining spatial structures of potential therapeutic compounds using x-ray crystallography. The scientists in Warsaw also use electron microscopy.
Time is of the essence
An important element of the project is to virtually identify known drugs which have been confirmed as being safe in humans. “This means the given molecule can be brought into use more quickly. It is also crucial that devising a complete platform for designing new drugs allows us to rapidly respond to any epidemics or pandemics in the future,” stresses Dr. Nowotny.
Timescale
The Exscalate4CoV project is due to be launched on 1 April 2020 at the latest. It is worth noting that drug discovery and development is a difficult, arduous and slow process. Finding a treatment for the coronavirus SARS-CoV-2 is likely to take at least months and perhaps years. The Warsaw group will receive over 70,000 euro in funding. Financing is provided by the European Commission as part of the Horizon 2020 program.
Protein Structure Laboratory
Dr. Marcin Nowotny’s group has been active for 12 years. The team specializes in molecular biology and works with the pharmaceutical industry on drug discovery and development. The researchers mainly use two methods – protein crystallography and, more recently, cryoelectronic microscopy – to visualize biological molecules (proteins, nucleic acids and their complexes) with a high degree of precision on the level of individual atoms. This helps them understand how these molecules function in healthy cells and under disease conditions.
Dr. Marcin Nowotny’s group operates as part of the PAS International Institute for Molecular and Cellular Biology.
Source: International Institute for Molecular and Cellular Biology
Published on 24 March 2020
