NECESSITY-New chemical entities modulating SARSCoV2 activity

Enzymes play a pivotal role in the propagation of viruses, their inhibition is a hallmark in established therapies e.g. against HIV-Infection. Among thousands of enzyme binding molecules, only a limited number is suitable as a drug. Under this international proposal three research sites teamed up to take the challenge of finding inhibitors based on the exactly known 3d structure of a SARS-CoV-2 enzyme. Vladimir Cryštof and his team (Olmütz/CZ) synthesize about 9,000 compounds which are tested by Christian Filer at the Helmholtz Center (Berlin/D) via differential X-ray diffraction in a high throughput mode for binding to a SARS-CoV-2 enzyme. In the FWF-funded project part the co-authors and research partners Theresia Dunzendorfer- Matt (Innsbruck Medical University) and Eduard Stefan (University of Innsbruck) will analyze preselected molecules in a reiterative process for interaction and inhibition in test tubes and in cultivated cells. Substances are filtered according to efficacy in vitro, specificity in a biosensor system, and development of resistance and finally screened by the virologist Christian Drosten (Charité Berlin/D). Aim of this project is the allocation of selected molecules as starting material for therapeutic compounds. The designed partially automated pipeline can in principle also be adapted to the development of other drugs. 2022-05-11created by TDMpage 1 1