Abstract
The SARS-CoV-2 main protease (M pro ) is a medicinal chemistry target for COVID-19 treatment. Given the clinical efficacy of β-lactams as inhibitors of bacterial nucleophilic enzymes, they are of interest as inhibitors of viral nucleophilic serine and cysteine proteases. We describe the synthesis of penicillin derivatives which are potent M pro inhibitors and investigate their mechanism of inhibition using mass spectrometric and crystallographic analyses. The results suggest that β-lactams have considerable potential as M pro inhibitors via a mechanism involving reaction with the nucleophilic cysteine to form a stable acyl-enzyme complex as shown by crystallographic analysis. The results highlight the potential for inhibition of viral proteases employing nucleophilic catalysis by β-lactams and related acylating agents.
【초록키워드】 COVID-19, Treatment, protease, inhibitors, SARS-CoV-2 main protease, COVID-19 treatment, inhibitor, synthesis, Enzymes, mechanism, Bacterial, Clinical efficacy, Analysis, cysteine, penicillin, Serine, reaction, cysteine proteases, complex, M pro, derivative, highlight, crystallographic analyses, mass spectrometric, shown, analyses, nucleophilic, 【제목키워드】 derivative, the SARS-CoV-2,