Penicillin Derivatives Inhibit the SARS-CoV-2 Main Protease by Reaction with Its Nucleophilic Cysteine
Tika R. Malla, Lennart Brewitz, Dorian-Gabriel Muntean, Hiba Aslam, David Owen, E. Salah, Anthony Tumber, Petra Lukacik, Claire Strain‐Damerell, Halina Mikolajek, Martin Walsh, Christopher J. Schofield
Abstract
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.
Topics & Concepts
ChemistryNucleophilePenicillinCysteineCysteine proteaseProteaseVirologyCombinatorial chemistryAntibioticsBiochemistryEnzymeCatalysisBiologySynthesis and biological activityComputational Drug Discovery MethodsHepatitis C virus research