“Our Existing Basic Research Provides a Solid Starting Point for Further Work”
Preventing the coronavirus from binding to host cells and fusing with them, and thus from spreading through the body, is the focus of current research by the structural biochemists at Jülich’s Institute of Biological Information Processing (IBI). More precisely, they are developing a ligand – a specific binding molecule – that displaces a certain binding protein of the virus from the receptor of the host cell. An interview with Prof. Dieter Willbold, the director of the institute
What makes IBI so well placed for research into the coronavirus?
Over the past 15 years, we have developed a whole range of completely new strategies, methods, and technologies for manipulating proteins’ 3D structure and thus their function, which are now available to the institute and the two spin-off companies Priavoid and attyloid. This has allowed us, for example, to develop a candidate drug that breaks down toxic and elusive Abeta oligomers into their harmless monomer building blocks and thus directly destroys the pathogenic elements. By contrast, manipulating a single viral protein is much simpler. What’s more, during the 2002–2003 SARS pandemic we conducted research into the structure and function of some of the proteins in the version of coronavirus that was spreading at that time. All this is to say that our existing basic research provides a solid starting point for further work.
You are pursuing various avenues in researching the coronavirus. Can you outline them?
The coronavirus uses a particular protein, called a “spike protein”, to bind to a human cell via a human protein called “ACE2” – and ultimately to transfer its genetic information. We are developing a molecule that binds to the spike protein and blocks its binding site for ACE2. This means that the virus can no longer dock to the cell surface and fuse with the host cell. Using NMR spectroscopy, we hope to decode the 3D structure of a small but very important viral protein and, in parallel, develop a molecule to inhibit it, so that the virus cannot continue to reproduce in a cell that has already been infected. A third project is investigating how a viral enzyme needed by the virus for reproduction can be inhibited. To this end, my colleague Valentin Gordeliy and his working group at IBI-7 have begun clarifying the atomic structure of the viral proteins “M”, “E”, and “3a”, in order to make structure-based drug design possible. Elsewhere, my colleague Birgit Strodel, who also works at IBI-7, has already carried out virtual drug screening using Jülich’s supercomputer.
How can the results be used?
Based on this research, we can develop an active substance that moderates or even prevents a severe illness in case of infection. But it should be made clear to everyone that it takes several years to go from laboratory trials to a useful drug, far too long for the current pandemic. Yet it is important to keep up the intensive research into the virus that causes COVID-19. Viruses can mutate and recur in a modified form, which means we need effective remedies. In the current pandemic, I am pinning my hopes on antiviral drugs that are already available and are being tested in many places around the world for their effectiveness in treating the novel coronavirus.
Prof. Dieter Willbold
Tel.: +49 2461 61-2100