Luminescent Assay for the Screening of SARS-CoV-2 MPro Inhibitors

Daan Sondag; Jona Merx; Emiel Rossing; Thomas J Boltje; Dennis W P M Löwik; Frank H T Nelissen; Mark van Geffen; Cornelis van 't Veer; Waander L van Heerde; Floris P J T Rutjes

doi:10.1002/cbic.202200190

Luminescent Assay for the Screening of SARS-CoV-2 M^Pro Inhibitors

Chembiochem. 2022 Aug 3;23(15):e202200190. doi: 10.1002/cbic.202200190. Epub 2022 Jun 14.

Affiliations

¹ Institute for Molecules and Materials, Radboud University, 6525, AJ Nijmegen, The Netherlands.
² Enzyre BV, Novio Tech Campus Transistorweg 5-i, 6534, AT Nijmegen, The Netherlands.
³ Department of Haematology, Radboud University Medical Centre, Nijmegen, The Netherlands) and Haemophilia Treatment Centre Nijmegen Eindhoven Maastricht (HTC-NEM) (The Netherlands.

Abstract

Since the outbreak of SARS-CoV-2 in December 2019 millions of infections have been reported globally. The viral chymotrypsin-like main protease (M^Pro ) exhibits a crucial role in viral replication and represents a relevant target for antiviral drug development. In order to screen potential M^Pro inhibitors we developed a luminescent assay using a peptide based probe containing a cleavage site specific for M^Pro . This assay was validated showing IC₅₀ values similar to those reported in the literature for known M^Pro inhibitors and can be used to screen new inhibitors.

Keywords: enzymes; imaging agents; inhibitors; luminescence.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / pharmacology
COVID-19 Drug Treatment*
Coronavirus 3C Proteases
Cysteine Endopeptidases
Humans
Luminescent Measurements
Molecular Docking Simulation
Protease Inhibitors / pharmacology
SARS-CoV-2*
Viral Nonstructural Proteins

Substances

Antiviral Agents
Protease Inhibitors
Viral Nonstructural Proteins
Cysteine Endopeptidases
Coronavirus 3C Proteases