C6-Alkoxy substituted penicillins are potent non-covalently binding inhibitors of the SARS-CoV-2 main protease

2025/01/01 by Dorian-Gabriel Muntean, Wojtek Treyde, Linda Kinena +5 · 1 voice · 1 citation
Biochemistry, Genetics and Molecular Biology · Chemistry · #Antibiotic Resistance in Bacteria #Pharmacological Receptor Mechanisms and Effects #Synthesis of β-Lactam Compounds

paper · pdf · doi:10.1039/d5md00789e

openalex publication_date 2025/01/01 · openalex created_date 2025/10/28 · openalex updated_date 2026/07/23

Abstract

covalent reaction of their β-lactam with a nucleophilic serine in their transpeptidase targets to give an acyl-enzyme complex. The results imply penicillin derivatives can be developed to inhibit enzymes via mechanisms other than formation of stable acyl-enzyme complexes.

Citations

• Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors
• An oral non-covalent non-peptidic inhibitor of SARS-CoV-2 Mpro ameliorates viral replication and pathogenesis in vivo
• Discovery of the Clinical Candidate S-892216 : A Second-Generation of SARS-CoV-2 3CL Protease Inhibitorfor Treating COVID-19
• Alkyne Derivatives of SARS-CoV-2 Main Protease Inhibitors Including Nirmatrelvir Inhibit by Reacting Covalently with the Nucleophilic Cysteine
• Silaproline-bearing nirmatrelvir derivatives are potent inhibitors of the SARS-CoV-2 main protease highlighting the value of silicon-derivatives in structure-activity-relationship studies

Cited by

• Cephalosporins are potent SARS-CoV-2 main protease inhibitors

Discussions

• Thrilled to see our work on β-lactams and SARS-CoV-2 Mpro published in @rscmedchem.rsc.org! It’s been a pleasure contributing the computational modelling to this collaboration, which highlights how su [bsky, 3 points, 0 comments]

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