Inhibitor potency and assay conditions: A case study on SARS-CoV-2 main protease
| Autor: | Christian D. Klein, Mira A. M. Behnam |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Letter
Stereochemistry medicine.medical_treatment Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Antiviral Agents chemistry.chemical_compound Endopeptidases medicine Humans Potency Virtual screening Multidisciplinary Protease SARS-CoV-2 COVID-19 Substrate (chemistry) Biological Sciences Atazanavir Biophysics and Computational Biology Förster resonance energy transfer chemistry EDANS Peptide Hydrolases medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Li et al. (1) report known drugs as inhibitors of the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The compounds, including atazanavir, were initially identified by virtual screening, followed by fluorescence resonance energy transfer (FRET)-based biochemical inhibition assays. In this letter, we demonstrate that the inhibitory activity achieved in enzymatic assays by the compounds is sensitive to the conditions used. This observation supports the proposed conformational selection paradigm for SARS-CoV-2 Mpro (2). Using an Mpro with C-terminal His-tag and the FRET substrate Abz-VVTLQ/SGDap(Dnp)R-OH (3), atazanavir showed no or minimal inhibition under all studied conditions, including the buffer used by Li et al. (1) This point was previously raised by Ma and Wang (4), and, in comparison to their substrate Dabcyl-KTSAVLQ/SGFRKME(Edans) (5), our shorter substrate renders an influence of substrate length less likely and pinpoints the difference in … [↵][1]1To whom correspondence may be addressed. Email: mira.behnam{at}uni-heidelberg.de or c.klein{at}uni-heidelberg.de. [1]: #xref-corresp-1-1 |
| Databáze: | OpenAIRE |
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