Screening of electrophilic compounds yields an aziridinyl peptide as new active-site directed SARS-CoV main protease inhibitor

The coronavirus main protease, M(pro), is considered a major target for drugs suitable to combat coronavirus infections including the severe acute respiratory syndrome (SARS). In this study, comprehensive HPLC- and FRET-substrate-based screenings of various electrophilic compounds were performed to...

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Autores principales: Martina, Erika, Stiefl, Nikolaus, Degel, Björn, Schulz, Franziska, Breuning, Alexander, Schiller, Markus, Vicik, Radim, Baumann, Knut, Ziebuhr, John, Schirmeister, Tanja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2005
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127417/
https://www.ncbi.nlm.nih.gov/pubmed/16216498
http://dx.doi.org/10.1016/j.bmcl.2005.09.012
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author Martina, Erika
Stiefl, Nikolaus
Degel, Björn
Schulz, Franziska
Breuning, Alexander
Schiller, Markus
Vicik, Radim
Baumann, Knut
Ziebuhr, John
Schirmeister, Tanja
author_facet Martina, Erika
Stiefl, Nikolaus
Degel, Björn
Schulz, Franziska
Breuning, Alexander
Schiller, Markus
Vicik, Radim
Baumann, Knut
Ziebuhr, John
Schirmeister, Tanja
author_sort Martina, Erika
collection PubMed
description The coronavirus main protease, M(pro), is considered a major target for drugs suitable to combat coronavirus infections including the severe acute respiratory syndrome (SARS). In this study, comprehensive HPLC- and FRET-substrate-based screenings of various electrophilic compounds were performed to identify potential M(pro) inhibitors. The data revealed that the coronaviral main protease is inhibited by aziridine- and oxirane-2-carboxylates. Among the trans-configured aziridine-2,3-dicarboxylates the Gly-Gly-containing peptide 2c was found to be the most potent inhibitor.
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spelling pubmed-71274172020-04-08 Screening of electrophilic compounds yields an aziridinyl peptide as new active-site directed SARS-CoV main protease inhibitor Martina, Erika Stiefl, Nikolaus Degel, Björn Schulz, Franziska Breuning, Alexander Schiller, Markus Vicik, Radim Baumann, Knut Ziebuhr, John Schirmeister, Tanja Bioorg Med Chem Lett Article The coronavirus main protease, M(pro), is considered a major target for drugs suitable to combat coronavirus infections including the severe acute respiratory syndrome (SARS). In this study, comprehensive HPLC- and FRET-substrate-based screenings of various electrophilic compounds were performed to identify potential M(pro) inhibitors. The data revealed that the coronaviral main protease is inhibited by aziridine- and oxirane-2-carboxylates. Among the trans-configured aziridine-2,3-dicarboxylates the Gly-Gly-containing peptide 2c was found to be the most potent inhibitor. Elsevier Ltd. 2005-12-15 2005-10-10 /pmc/articles/PMC7127417/ /pubmed/16216498 http://dx.doi.org/10.1016/j.bmcl.2005.09.012 Text en Copyright © 2005 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Martina, Erika
Stiefl, Nikolaus
Degel, Björn
Schulz, Franziska
Breuning, Alexander
Schiller, Markus
Vicik, Radim
Baumann, Knut
Ziebuhr, John
Schirmeister, Tanja
Screening of electrophilic compounds yields an aziridinyl peptide as new active-site directed SARS-CoV main protease inhibitor
title Screening of electrophilic compounds yields an aziridinyl peptide as new active-site directed SARS-CoV main protease inhibitor
title_full Screening of electrophilic compounds yields an aziridinyl peptide as new active-site directed SARS-CoV main protease inhibitor
title_fullStr Screening of electrophilic compounds yields an aziridinyl peptide as new active-site directed SARS-CoV main protease inhibitor
title_full_unstemmed Screening of electrophilic compounds yields an aziridinyl peptide as new active-site directed SARS-CoV main protease inhibitor
title_short Screening of electrophilic compounds yields an aziridinyl peptide as new active-site directed SARS-CoV main protease inhibitor
title_sort screening of electrophilic compounds yields an aziridinyl peptide as new active-site directed sars-cov main protease inhibitor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127417/
https://www.ncbi.nlm.nih.gov/pubmed/16216498
http://dx.doi.org/10.1016/j.bmcl.2005.09.012
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