A dual covalent binder for labelling and inhibiting serine and metallo-carbapenemases

Abstract

The continuous emergence of multi-drug resistant pathogens co-expressing serine and metallo-carbapenemases seriously threatens the efficacy of carbapenem. Here, we report the first SeCN-derived dual inhibitor of serine and metallo-carbapenemases with IC₅₀ values ranging from 0.0038 to 1.27 μg mL⁻¹. The inhibitor was shown to form covalent bonds with Cys221 of NDM-1 and Ser70 of KPC-2, respectively, achieving selective labelling and cross-class inhibition for carbapenemases. Our results provide a potential strategy to develop clinically useful dual inhibitors targeting serine and metallo-carbapenemases to combat superbugs.