Peptide-β-lactam inhibitors of dengue and West Nile virus NS2B-NS3 protease display two distinct binding modes.

  title={Peptide-$\beta$-lactam inhibitors of dengue and West Nile virus NS2B-NS3 protease display two distinct binding modes.},
  author={Tonko Dra{\vz}i{\'c} and Sara Kopf and James Corridan and Mila M. Leuthold and Branimir Berto{\vs}a and Christian D P Klein},
  journal={Journal of medicinal chemistry},
The β-lactam ring represents a valuable moiety that can induce covalent binding of an inhibitor to its target. In this study, we explored di- and tripeptides with β-lactam electrophilic warheads as inhibitors of dengue and West Nile virus NS2B-NS3 protease. Tripeptides with a (3S)-β-lactam moiety displayed highest activity, with IC50 and EC50 values in the lower micromolar range in biochemical and cellular assays. The activity against dengue protease was in general higher than against West Nile… 
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