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Action of Dipeptidyl Peptidase-4 Inhibitors on SARS-CoV-2 Main Protease.

ABSTRACT: In a recent publication, Eleftheriou et al. proposed that inhibitors of dipeptidyl peptidase-4 (DPP-4) are 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 the 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 the 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 .

SUBMITTER: Nar H

PROVIDER: S-EPMC8248156 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Action of Dipeptidyl Peptidase-4 Inhibitors on SARS-CoV-2 Main Protease.

Nar Herbert H Schnapp Gisela G Hucke Oliver O Hardman Timothy C TC Klein Thomas T

ChemMedChem 20210217 9

In a recent publication, Eleftheriou et al. proposed that inhibitors of dipeptidyl peptidase-4 (DPP-4) are functional inhibitors of the main protease (M<sup>pro</sup> ) 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 the inhibition of M<sup>pro</sup> catalytic activity in the presence of four different commerci ...[more]

PMID: 33348462

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