HZB coordinates European collaboration to develop active agents against Corona
The MX team at BESSY II specialises in analysing protein structures. This can also accelerate the development of drugs against COVID-19. © HZB
X-ray structure analysis at BESSY II enables the systematic testing of many thousands of molecules that could inhibit the reproduction and virulence of SARS-CoV2 viruses. Now, a team at HZB with partners from Austria and the Czech Republic has set up the NECESSITY project to investigate more than 8000 compounds in a high-throughput procedure and develop active agents against COVID-19.
The COVID-19 pandemic is far from over. Despite the rapid development of vaccines, it is not possible, for various reasons, to give everyone lasting protection through vaccination quickly enough. But so far, there are hardly any effective drugs for patients severely affected by COVID-19. Therapy is mainly limited to the administration of steroid drugs to control the immune reaction and artificial respiration.
Researchers around HZB-scientist Dr. Christian Feiler have initiated a three-party European research study termed NECESSITY, led by project partner Prof. Dr. Klaus Scheffzek (Med. University Innsbruck, Austria). Their goal is to investigate detailed interactions between Sars-CoV-2 proteins and chemical compounds developed and provided by Dr. Vladimír Kryštof (Palacký University Olomouc, the Czech Republic), using structural and biochemical approaches. X-ray structure analysis at BESSY II enables the systematic testing of many thousands of molecules that could inhibit the reproduction and virulence of SARS-CoV2 viruses. This research is funded by the Austrian Science Fund (FWF), the German Research Foundation (DFG), and the Czech Science Foundation (GACR).
At the light source BESSY II, which is operated by HZB, the structural analysis of macromolecules provides a fantastic tool to accelerate the development of effective substances against the SARS-CoV2 virus. The three-dimensional structure of the so-called viral main protease was determined at BESSY II for the first time at the beginning of 2020. This enzyme is indispensable for virus replication. However, it is not sufficient to investigate this one target, which is why several viral target proteins are being addressed in the NECESSITY project. The consortium will explore more than 8000 compounds at the MX-beamlines of BESSY II in a high-throughput procedure and identify substances from them that could dock to the main protease of SARS-CoV-2 or other target proteins. These drug-like candidates originate from a unique library generated and collected by Dr. Vladimír Kryštof, Palacký University Olomouc. All compounds are either already approved for the treatment of other diseases or are in various clinical phases. If hits were to come out of this, it would be possible to develop drugs against COVID-19 remarkably quickly. Prof. Dr. Klaus Scheffzek and his team at the Medical University in Innsbruck can investigate the hit compounds in detail using biophysical methods and initiate the first virological studies. Prof. Dr. Christian Drosten, Director of the Institute of Virology at Charité Berlin, and other experts are also on board as advisors and partners.
"In the NECESSITY project, we bring together expertise from different fields," says Feiler. "Together, we have planned a very efficient interdisciplinary workflow to identify antiviral substances that can be used as effective drugs against COVID-19 and beyond as quickly as possible."
The project is funded by the German Research Foundation and the corresponding funding organizations in Austria and the Czech Republic for 36 months with almost 800,000 Euros.
- BESSY II: Phosphorous chains – a 1D material with 1D electronic propertiesFor the first time, a team at BESSY II has succeeded in demonstrating the one-dimensional electronic properties of a material through a highly refined experimental process. The samples consisted of short chains of phosphorus atoms that self-organise at specific angles on a silver substrate. Through sophisticated analysis, the team was able to disentangle the contributions of these differently aligned chains. This revealed that the electronic properties of each chain are indeed one-dimensional. Calculations predict an exciting phase transition to be expected as soon as these chains are more closely packed. While material consisting of individual chains with longer distances is semiconducting, a very dense chain structure would be metallic.
- Did marine life in the palaeocene use a compass?Some ancient marine organisms produced mysterious magnetic particles of unusually large size, which can now be found as fossils in marine sediments. An international team has succeeded in mapping the magnetic domains on one of such ‘giant magnetofossils’ using a sophisticated method at the Diamond X-ray source. Their analysis shows that these particles could have allowed these organisms to sense tiny variations in both the direction and intensity of the Earth’s magnetic field, enabling them to geolocate themselves and navigate across the ocean. The method offers a powerful tool for magnetically testing whether putative biological iron oxide particles in Mars samples have a biogenic origin.
- What vibrating molecules might reveal about cell biologyInfrared vibrational spectroscopy at BESSY II can be used to create high-resolution maps of molecules inside live cells and cell organelles in native aqueous environment, according to a new study by a team from HZB and Humboldt University in Berlin. Nano-IR spectroscopy with s-SNOM at the IRIS beamline is now suitable for examining tiny biological samples in liquid medium in the nanometre range and generating infrared images of molecular vibrations with nanometre resolution. It is even possible to obtain 3D information. To test the method, the team grew fibroblasts on a highly transparent SiC membrane and examined them in vivo. This method will provide new insights into cell biology.