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

Tika R. Malla, Anthony Tumber, Tobias John, Lennart Brewitz, Claire M. Strain-Damerell, David Owen, Petra Lukacik, H. T. Henry Chan, Pratheesh Maheswaran, E. Salah, Fernanda Duarte, Haitao Yang, Zihe Rao, Martin Austin Walsh, Christopher John Schofield · Chemical Communications · 2021

The main viral protease (Mpro) 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 Mpro assay. The results reveal some β-lactams, including penicillin esters, are active site reacting Mpro inhibitors, thus highlighting the potential of acylating agents for Mpro inhibition.

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