Conveners
COVID-19 Research
- Manfred Weiss (Macromolecular Crystallography, Helmholtz-Zentrum Berlin für Materialien und Energie (HZB-MX))
During this decade, protein crystallography has immensely increased the speed of structure determination, allowing now using this high resolution technology for experimental fragment screening and hit optimization. At the same time, family wide structural genomics efforts elucidated molecular details of entire protein families including the main drug target families such as protein kinases,...
Our work focuses on the identification of novel therapeutics against SARS-CoV-2. Using a HT screening approach, compound libraries of approved drugs are used for the discovery of inhibitors for enzymes of the coronavirus replication-transcription complex, followed by the structural determination of the enzyme-inhibitor complexes, revealing their binding mode. This approach is cost efficient,...
Structure-based design of new inhibitors of the SARS-CoV-2 main protease (Mpro) is discussed and corresponding crystal structures are described. Pharmacokinetics of frontrunner inhibitors are presented. The evolution of the Mpro from the original Wuhan strain via the Alpha, Beta, Delta, and Omicron variants of concern is followed in terms of three-dimensional (crystal) structures, enzymatic...
Here, we demonstrate the use of AlphaFold on proteins from SARS-CoV-2. While the solved structures only cover a part of the viral genome we have plenty of annotated protein-coding genes, which structures can now be predicted computationally. We discuss both the benefits as well as the potential shortcomings of these predictions and show how they can be combined with information from other...
