How to screen faster – Efficient identification of active ingredients against SARS-CoV-2 and chemical probes as inhibitors of the 3CL and PL proteases of coronaviruses
Up to now, classical enzyme assays with fluorogenic substrate have been used for the identification of drug candidates. However, this multi-step procedure can only be used for in vitro studies – potential candidates must be examined in a subsequent step with regard to important aspects such as a focus on the active site of the enzyme, the reactivity against proteins and their ability to cross cell membranes. In addition, the identification of promising candidates requires the exclusion of numerous off-targets.
Up to now, there is no method that can be performed directly in living cells, considering cell permeability at the same time, and that also allows the identification in complex mixtures. Thus, the conventional method of drug screening is a lengthy process and generally slow, particularly too slow in the case of an acute pandemic.
- Fast and effective drug screening for antiviral inhibitors without the time-consuming synthesis of libraries
- Realizable as a high-throughput procedure
- Inhibition of proteases before autocatalytic maturation
- Identification of potent enzyme inhibitors with cell permeability
- Suitable for non-proteolytic enzymes
- Small number of off-targets
More effective drug screening and fast, reliable drug candidate selection against viruses such as SARS-CoV-2 and other pathogens with similar proteases.
Find out more
Peñalver, L., Schmid, P., Szamosvári, D., Schildknecht, S., Globisch, C., Sawade, K., Peter, C. and Böttcher, T. (2021),
A Ligand Selection Strategy Identifies Chemical Probes Targeting the Proteases of SARS-CoV-2. Angew. Chem. Int. Ed.