Virus-specific proteases are essential for the cellular virus replication and are thus the focus for drug discovery strategies. Using a ligand selection strategy, chemical electrophilic probes were identified that target highly specifically the active site of these enzymes. Thus, even in live-cell models and complex cell samples, these probes can be used to detect proteases like the two SARS-CoV-2 proteases analysed in this study. Screening for identification of customized inhibitors is another application of this method. These drugs are more likely to be effective when used to treat infections. The method is suitable for high-throughput screening and for discovering inhibitors for a wide range of target proteins also beyond coronavirus proteases. A patent has been filed for the method.
A ligand selection strategy identifies chemical probes targeting the proteases of SARS‐CoV‐2
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