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However, it has not yet evolved into a medical intervention, mainly because most developed inhibitors target the zinc in IDE\u2019s catalytic site, potentially causing toxicity to other essential metalloproteases. Since IDE is a cellular receptor for the varicella\u2010zoster virus (VZV), we constructed a VZV\u2010based inhibitor. We computationally characterized its interaction site with IDE showing that the peptide specifically binds inside IDE's central cavity, however, not in close proximity to the zinc ion. We confirmed the peptide's effective inhibition on IDE activity in vitro and showed its efficacy in ameliorating insulin\u2010related defects in types 1 and 2 diabetes mouse models. In addition, we suggest that inhibition of IDE may ameliorate the pro\u2010inflammatory profile of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cells toward insulin. 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