Azapeptide activity-based probes for the SARS-CoV-2 main protease enable visualization of inhibition in infected cells.
Roeland VanhoutteMarta Barniol-XicotaWinston ChiuLaura VangeelDirk JochmansSteven De JongheHadeer ZidaneHaim M BarrNir LondonJohan NeytsSteven H L VerhelstPublished in: Chemical science (2023)
The COVID-19 pandemic has revealed the vulnerability of the modern, global society. With expected waves of future infections by SARS-CoV-2, treatment options for infected individuals will be crucial in order to decrease mortality and hospitalizations. The SARS-CoV-2 main protease is a validated drug target, for which the first inhibitor has been approved for use in patients. To facilitate future work on this drug target, we designed a solid-phase synthesis route towards azapeptide activity-based probes that are capped with a cysteine-reactive electrophile for covalent modification of the active site of M pro . This design led to the most potent ABP for M pro and one of the most potent inhibitors reported thus far. We demonstrate that this ABP can be used to visualize M pro activity and target engagement by drugs in infected cells.
Keyphrases
- sars cov
- induced apoptosis
- anti inflammatory
- respiratory syndrome coronavirus
- cell cycle arrest
- living cells
- small molecule
- ejection fraction
- newly diagnosed
- single molecule
- endoplasmic reticulum stress
- fluorescence imaging
- cardiovascular disease
- type diabetes
- climate change
- prognostic factors
- social media
- chronic kidney disease
- risk factors
- patient reported outcomes
- patient reported