Research in times of corona
More than a year after the start of the pandemic, the virus is still one step ahead of man. With mutations, SARS-CoV-2 has increased its pace, but science is hot on its heels. Mathematics, physics and supercomputers help to better understand the spread and properties of the virus in order to slow it down.
As long as much of the population is not vaccinated, reducing contact remains the sharpest weapon in the fight against the pandemic. Calculations by the Jülich Supercomputing Centre and the Frankfurt Institute for Advanced Studies show how strongly the “participation rate” affects the occurrence of infection:
A significant decline in new infections can only be achieved within a few weeks if contact restrictions are sufficiently strong and enough people adopt the rules. Based on the numbers in Germany in autumn 2020, the researchers assumed an R value of 1.5 and a 7-day incidence of 150 at the start of their simulations.
Scenario 1: One part of the population reduces physical contact by 75 per cent, while the other part does not change behaviour – in the first picture, 50 per cent join in, in the second 70 per cent and in the third 90 per cent. Only the last variant succeeds in significantly reducing the number of infections within weeks.
Szenario 2: Among the participating part of the population, physical contact is reduced by 50 per cent. Even at a rate of 90 per cent, the spread of infection is barely contained.
Computing power against SARS-CoV-2
Vaccination is going well. What is still missing, however, is an effective cure. In an international joint project with 18 institutions from seven European countries (Exscalate4Coronavirus), Jülich researchers are hunting for molecules that block central proteins of the coronavirus and, thus, its replication.
They are using the computing power of Europe’s largest supercomputer centres for this, including the Jülich Supercomputing Centre: within weeks, they had checked the effect of millions of molecules. In the process, the researchers have found a way to more accurately predict which molecules inhibit the main 3CL protease of SARS-CoV-2 in the computer model.
The 3CL protease is an enzyme that enables the virus to replicate.
The team has taken into account the extremely flexible 3D structure of the active enzyme centre, which is crucial for its function. They calculated the numerous formations that the centre can adopt and what possible inhibitors would have to look like in order to block it. Prof. Giulia Rossetti from the Institute of Neuroscience and Medicine (INM-9/IAS-5) and the Jülich Supercomputing Centre (JSC) says: “We have thus succeeded in identifying two new 3CL protease inhibitors. The method can also be applied to other proteins that have similarly flexible properties.”
3 questions for …
… Prof. Jörg Labahn and Dr. Aurel Radulescu. Both work at Jülich branch offices: Jörg Labahn, from the Centre for Structural Systems Biology, uses Germany’s most intense X-ray sources at the DESY research centre in Hamburg to decipher structures of central proteins in the virus. Aurel Radulescu, a staff member at the Jülich Centre for Neutron Science in Garching, uses the neutron scattering instruments at Heinz Maier-Leibnitz Zentrum to investigate nanoparticles that coat the novel messenger RNA vaccines.
What exactly are you researching?
Jörg Labahn: We are investigating three proteins: the spike protein, which the virus uses to enter the cell; another that is essential for replication; and a third one called NSP6, about which we still don’t know much, though.
Aurel Radulescu: OWithout a nanoparticle coating, the messenger RNA of the vaccine would be destroyed directly by the body’s own enzymes – even before it can be taken up by cells and its information be read. We want to know how to improve the packaging.
Which questions do the X-ray and neutron sources answer?
Jörg Labahn: With the help of X-ray structural analysis, we throw light on how the spike protein attaches to the cell. We also use it to study the structure of other corona proteins to find out how to block them and thus prevent the virus from replicating.
Aurel Radulescu: Neutron scattering characterises the internal organisation of nanoparticles. With this knowledge, we can assess whether a nanoparticle is suitable for introducing messenger RNA vaccines or other therapeutic agents into the cell.
Instead of a virus, these vaccines contain the building instructions for part of the virus in the form of messenger RNA. This causes the cells to produce the spike protein, which is then recognised by the body as “foreign” and attacked by the immune system.
What are the next goals?
Jörg Labahn: Of substances which have already been approved for therapeutic applications, we want to identify those that inhibit the functions of the viral target proteins. In the case of the membrane protein NSP6, it is also important to find out whether it is suitable as a target for medications.
Aurel Radulescu: Our results show that nanoparticles made of a combination of lipids and polymers significantly improve the transfer of messenger RNA into the cell. This can help to advance the further development of customised therapeutics and RNA vaccines.
TEXTS: Brigitte Stahl-Busse
PHOTOS: Kzenon/shutterstock.com, Matteo Migliorati/shutterstock.com, Forschungszentrum Jülich/Ralf-Uwe Limbach GRAPHICS: FIAS/Jan Fuhrmann