Volkswagen Foundation funds two new SARS-CoV-2 research projects
8 July 2021. The Volkswagen Foundation announced that it will fund two collaborative research projects on new COVID-19 therapeutic approaches with a total of around 1.4 million euros. The Target-RNA-antiV project will investigate how the gene regulation of the virus can be specifically disrupted (in collaboration with TU Darmstadt). The CoVmacro project will investigate how a viral protein that is important for virus replication can be blocked (together with RWTH Aachen, LMU Munich and Forschungszentrum Jülich). The projects will be supported for 36 months each.
Target-RNA-antiV focuses directly on the viral RNA genome in the search for active agents: The groups of Maike Windbergs, Harald Schwalbe (both Goethe University) and Julia Weigand (TU Darmstadt) are building on the work of the international COVID-19 NMR consortium, which has identified a total of 15 control elements in the genome of SARS-CoV-2. With their help, the virus directs the course of infection in the human cell. One of these control elements is the focus of "Target-RNA-antiV". It is a kind of switch that enables the virus to produce two different viral proteins from the same piece of genetic material (RNA pseudoknot element). The scientists will look for small molecules that block this switch so that the virus can no longer produce a number of important proteins. Promising drug candidates will then be sprayed onto 3D cell culture models of human lungs to test their potential applicability as therapeutics.
CoVmacro focuses on the viral protein nsP3, which SARS-CoV-2 uses to inhibit the cellular defense response. Previous work has already shown that a specific part of nsP3, the so-called macrodomain, can be targeted by medical drugs. With the help of the macrodomain, the virus ensures that cells no longer succeed in activating signaling pathways for stress and defense reactions. Biochemically, the viral macrodomain prevents the sugar ADP-ribose from being attached to corresponding cellular signal proteins in order to activate the signal chain. The groups of Stefan Knapp (Goethe University), Bernhard Lüscher and Patricia Korn (both RWTH-Aachen), Andreas Ladurner (LMU Munich) and Giulia Rossetti (Forschungszentrum Jülich) are searching together in this new project for small molecules that can inhibit the viral macrodomain and thus strengthen the cell's own defense. Since the macrodomain is structured in a very similar way in many other coronaviruses, hepatitis E viruses and alphaviruses (such as the chikungunya virus), this kind of treatment could also be effective against other diseases.
Contacts:
Target-RNA-antiV: Maike Windbergs (Buchmann Institute for Molecular Life Sciences and Institute for Pharmaceutical Technology, windbergs@em.uni-frankfurt.de) and Harald Schwalbe (Institute for Organic Chemistry and Chemical Biology and the Center for Biomolecular Magnetic Resonance, schwalbe@nmr.uni-frankfurt.de), Goethe University, Frankfurt/Main
CoVmacro: Stefan Knapp, Institute for Pharmaceutical Technology and Buchmann Institute for Molecular Life Sciences, Goethe University, Frankfurt/Main, knapp@pharmchem.uni-frankfurt.de, www.uni-frankfurt.de/53483664/Knapp