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In a recent publication in this journal Eleftheriou et al. proposed inhibitors of dipeptidyl peptidase-4 (DPP-4) to be functional inhibitors of the main protease (M pro ) of SARS-CoV-2. Their predictions prompted the authors to suggest linagliptin, a DPP-4 inhibitor and approved anti-diabetes drug, as a repurposed drug candidate against the ongoing COVID-19 pandemic. We used an enzymatic assay measuring inhibition of M pro catalytic activity in the presence of four different commercially available gliptins (linagliptin, sitagliptin, alogliptin and saxagliptin) and several structural analogues of linagliptin to study binding of DPP-4 inhibitors to M pro and their functional activity. We show here that DPP-4 inhibitors like linagliptin, other gliptins and structural analogues are inactive against M pro .
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Action of dipeptidyl peptidase-4 inhibitors on SARS-CoV-2 main protease.
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