Based on investigations on the biochemistry of the protease-inhibitor interaction and inhibition kinetics, we are designing and synthesizing tailored inhibitors for therapeutically relevant proteases and the main protease of SARS-CoV-2. We equipped synthetic inhibitors with reporter groups to assemble activity-based probes as valuable tool compounds to study target enzymes in a pathophysiological context. Proteolysis targeting chimeras (PROTACs) are bifunctional small molecules, which simultaneously bind a target protein and an E3 ubiquitin ligase. We are developing PROTACs, e.g. for the self-directed ubiquitination of ligases or the degradation of kinases, thus significantly contributing to this pioneering new modality in drug discovery.