Mass spectrometry reveals potential of β-lactams as SARS-CoV-2 Mpro inhibitors

Tika R. Malla; Anthony Tumber; Tobias John; Lennart Brewitz; Claire Strain-Damerell; C David Owen; Petra Lukacik; H. T. Henry Chan; Pratheesh Maheswaran; Eidarus Salah; Fernanda Duarte; Haitao Yang; Zihe Rao; Martin A. Walsh; Christopher J. Schofield

doi:10.1039/D0CC06870E

Mass spectrometry reveals potential of β-lactams as SARS-CoV-2 M^pro inhibitors†

Tika R. Malla,

^a Anthony Tumber,^a Tobias John,

^a Lennart Brewitz,

^a Claire Strain-Damerell,

^bc C David Owen,

^bc Petra Lukacik,

^bc H. T. Henry Chan,

^a Pratheesh Maheswaran,

^a Eidarus Salah,^a Fernanda Duarte,

^a Haitao Yang,^d Zihe Rao,^d Martin A. Walsh

^bc and Christopher J. Schofield

*^a

Author affiliations

* Corresponding authors

^a Chemistry Research Laboratory, Department of Chemistry, 12 Mansfield Road, Oxford, UK
E-mail: christopher.schofield@chem.ox.ac.uk

^b Diamond Light Source, Harwell Science & Innovation Campus, Didcot, Oxfordshire OX11 0DE, UK

^c Research Complex at Harwell, Harwell Science & Innovation Campus, Didcot, Oxfordshire OX11 0FA, UK

^d Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China

Abstract

The main viral protease (M^pro) of SARS-CoV-2 is a nucleophilic cysteine hydrolase and a current target for anti-viral chemotherapy. We describe a high-throughput solid phase extraction coupled to mass spectrometry M^pro assay. The results reveal some β-lactams, including penicillin esters, are active site reacting M^pro inhibitors, thus highlighting the potential of acylating agents for M^pro inhibition.

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Chemical Communications

Mass spectrometry reveals potential of β-lactams as SARS-CoV-2 M^pro inhibitors†

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Chemical Communications

Mass spectrometry reveals potential of β-lactams as SARS-CoV-2 Mpro inhibitors†

Abstract

Supplementary files

Article information

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Mass spectrometry reveals potential of β-lactams as SARS-CoV-2 Mpro inhibitors

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Mass spectrometry reveals potential of β-lactams as SARS-CoV-2 M^pro inhibitors†

Mass spectrometry reveals potential of β-lactams as SARS-CoV-2 M^pro inhibitors