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Design, synthesis and in vitro evaluation of novel SARS-CoV-2 3CL(pro) covalent inhibitors

Severe diseases such as the ongoing COVID-19 pandemic, as well as the previous SARS and MERS outbreaks, are the result of coronavirus infections and have demonstrated the urgent need for antiviral drugs to combat these deadly viruses. Due to its essential role in viral replication and function, 3CL(...

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Autores principales: Stille, Julia K., Tjutrins, Jevgenijs, Wang, Guanyu, Venegas, Felipe A., Hennecker, Christopher, Rueda, Andrés M., Sharon, Itai, Blaine, Nicole, Miron, Caitlin E., Pinus, Sharon, Labarre, Anne, Plescia, Jessica, Burai Patrascu, Mihai, Zhang, Xiaocong, Wahba, Alexander S., Vlaho, Danielle, Huot, Mitchell J., Schmeing, T. Martin, Mittermaier, Anthony K., Moitessier, Nicolas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Masson SAS. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8665847/
https://www.ncbi.nlm.nih.gov/pubmed/34995923
http://dx.doi.org/10.1016/j.ejmech.2021.114046
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author Stille, Julia K.
Tjutrins, Jevgenijs
Wang, Guanyu
Venegas, Felipe A.
Hennecker, Christopher
Rueda, Andrés M.
Sharon, Itai
Blaine, Nicole
Miron, Caitlin E.
Pinus, Sharon
Labarre, Anne
Plescia, Jessica
Burai Patrascu, Mihai
Zhang, Xiaocong
Wahba, Alexander S.
Vlaho, Danielle
Huot, Mitchell J.
Schmeing, T. Martin
Mittermaier, Anthony K.
Moitessier, Nicolas
author_facet Stille, Julia K.
Tjutrins, Jevgenijs
Wang, Guanyu
Venegas, Felipe A.
Hennecker, Christopher
Rueda, Andrés M.
Sharon, Itai
Blaine, Nicole
Miron, Caitlin E.
Pinus, Sharon
Labarre, Anne
Plescia, Jessica
Burai Patrascu, Mihai
Zhang, Xiaocong
Wahba, Alexander S.
Vlaho, Danielle
Huot, Mitchell J.
Schmeing, T. Martin
Mittermaier, Anthony K.
Moitessier, Nicolas
author_sort Stille, Julia K.
collection PubMed
description Severe diseases such as the ongoing COVID-19 pandemic, as well as the previous SARS and MERS outbreaks, are the result of coronavirus infections and have demonstrated the urgent need for antiviral drugs to combat these deadly viruses. Due to its essential role in viral replication and function, 3CL(pro) (main coronaviruses cysteine-protease) has been identified as a promising target for the development of antiviral drugs. Previously reported SARS-CoV 3CL(pro) non-covalent inhibitors were used as a starting point for the development of covalent inhibitors of SARS-CoV-2 3CL(pro). We report herein our efforts in the design and synthesis of submicromolar covalent inhibitors when the enzymatic activity of the viral protease was used as a screening platform.
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spelling pubmed-86658472021-12-14 Design, synthesis and in vitro evaluation of novel SARS-CoV-2 3CL(pro) covalent inhibitors Stille, Julia K. Tjutrins, Jevgenijs Wang, Guanyu Venegas, Felipe A. Hennecker, Christopher Rueda, Andrés M. Sharon, Itai Blaine, Nicole Miron, Caitlin E. Pinus, Sharon Labarre, Anne Plescia, Jessica Burai Patrascu, Mihai Zhang, Xiaocong Wahba, Alexander S. Vlaho, Danielle Huot, Mitchell J. Schmeing, T. Martin Mittermaier, Anthony K. Moitessier, Nicolas Eur J Med Chem Article Severe diseases such as the ongoing COVID-19 pandemic, as well as the previous SARS and MERS outbreaks, are the result of coronavirus infections and have demonstrated the urgent need for antiviral drugs to combat these deadly viruses. Due to its essential role in viral replication and function, 3CL(pro) (main coronaviruses cysteine-protease) has been identified as a promising target for the development of antiviral drugs. Previously reported SARS-CoV 3CL(pro) non-covalent inhibitors were used as a starting point for the development of covalent inhibitors of SARS-CoV-2 3CL(pro). We report herein our efforts in the design and synthesis of submicromolar covalent inhibitors when the enzymatic activity of the viral protease was used as a screening platform. Elsevier Masson SAS. 2022-02-05 2021-12-11 /pmc/articles/PMC8665847/ /pubmed/34995923 http://dx.doi.org/10.1016/j.ejmech.2021.114046 Text en © 2021 Elsevier Masson SAS. 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
Stille, Julia K.
Tjutrins, Jevgenijs
Wang, Guanyu
Venegas, Felipe A.
Hennecker, Christopher
Rueda, Andrés M.
Sharon, Itai
Blaine, Nicole
Miron, Caitlin E.
Pinus, Sharon
Labarre, Anne
Plescia, Jessica
Burai Patrascu, Mihai
Zhang, Xiaocong
Wahba, Alexander S.
Vlaho, Danielle
Huot, Mitchell J.
Schmeing, T. Martin
Mittermaier, Anthony K.
Moitessier, Nicolas
Design, synthesis and in vitro evaluation of novel SARS-CoV-2 3CL(pro) covalent inhibitors
title Design, synthesis and in vitro evaluation of novel SARS-CoV-2 3CL(pro) covalent inhibitors
title_full Design, synthesis and in vitro evaluation of novel SARS-CoV-2 3CL(pro) covalent inhibitors
title_fullStr Design, synthesis and in vitro evaluation of novel SARS-CoV-2 3CL(pro) covalent inhibitors
title_full_unstemmed Design, synthesis and in vitro evaluation of novel SARS-CoV-2 3CL(pro) covalent inhibitors
title_short Design, synthesis and in vitro evaluation of novel SARS-CoV-2 3CL(pro) covalent inhibitors
title_sort design, synthesis and in vitro evaluation of novel sars-cov-2 3cl(pro) covalent inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8665847/
https://www.ncbi.nlm.nih.gov/pubmed/34995923
http://dx.doi.org/10.1016/j.ejmech.2021.114046
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