A Ligand Selection Strategy Identifies Chemical Probes Targeting the Proteases of SARS-CoV-2.
Angew Chem Int Ed Engl
; 60(12): 6799-6806, 2021 03 15.
Article
in English
| MEDLINE | ID: covidwho-985937
ABSTRACT
Activity-based probes are valuable tools for chemical biology. However, finding probes that specifically target the active site of an enzyme remains a challenging task. Herein, we present a ligand selection strategy that allows to rapidly tailor electrophilic probes to a target of choice and showcase its application for the two cysteine proteases of SARS-CoV-2 as proof of concept. The resulting probes were specific for the active site labeling of 3CLpro and PLpro with sufficient selectivity in a live cell model as well as in the background of a native human proteome. Exploiting the probes as tools for competitive profiling of a natural product library identified salvianolic acid derivatives as promising 3CLpro inhibitors. We anticipate that our ligand selection strategy will be useful to rapidly develop customized probes and discover inhibitors for a wide range of target proteins also beyond corona virus proteases.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Molecular Probes
/
Cysteine Proteinase Inhibitors
/
Molecular Probe Techniques
/
Small Molecule Libraries
/
Coronavirus 3C Proteases
/
Coronavirus Papain-Like Proteases
/
SARS-CoV-2
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
Angew Chem Int Ed Engl
Year:
2021
Document Type:
Article
Affiliation country:
Anie.202016113
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