Discovery of highly potent SARS-CoV-2 M(pro) inhibitors based on benzoisothiazolone scaffold

The COVID-19 pandemic has drastically impacted global economies and public health. Although vaccine development has been successful, it was not sufficient against more infectious mutant strains including the Delta variant indicating a need for alternative treatment strategies such as small molecular...

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Autores principales: Chen, Weixiong, Feng, Bo, Han, Sheng, Wang, Peipei, Chen, Wuhong, Zang, Yi, Li, Jia, Hu, Youhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8730469/
https://www.ncbi.nlm.nih.gov/pubmed/34998903
http://dx.doi.org/10.1016/j.bmcl.2022.128526
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author Chen, Weixiong
Feng, Bo
Han, Sheng
Wang, Peipei
Chen, Wuhong
Zang, Yi
Li, Jia
Hu, Youhong
author_facet Chen, Weixiong
Feng, Bo
Han, Sheng
Wang, Peipei
Chen, Wuhong
Zang, Yi
Li, Jia
Hu, Youhong
author_sort Chen, Weixiong
collection PubMed
description The COVID-19 pandemic has drastically impacted global economies and public health. Although vaccine development has been successful, it was not sufficient against more infectious mutant strains including the Delta variant indicating a need for alternative treatment strategies such as small molecular compound development. In this work, a series of SARS-CoV-2 main protease (M(pro)) inhibitors were designed and tested based on the active compound from high-throughput diverse compound library screens. The most efficacious compound (16b-3) displayed potent SARS-CoV-2 M(pro) inhibition with an IC(50) value of 116 nM and selectivity against SARS-CoV-2 M(pro) when compared to PL(pro) and RdRp. This new class of compounds could be used as potential leads for further optimization in anti COVID-19 drug discovery.
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spelling pubmed-87304692022-01-06 Discovery of highly potent SARS-CoV-2 M(pro) inhibitors based on benzoisothiazolone scaffold Chen, Weixiong Feng, Bo Han, Sheng Wang, Peipei Chen, Wuhong Zang, Yi Li, Jia Hu, Youhong Bioorg Med Chem Lett Article The COVID-19 pandemic has drastically impacted global economies and public health. Although vaccine development has been successful, it was not sufficient against more infectious mutant strains including the Delta variant indicating a need for alternative treatment strategies such as small molecular compound development. In this work, a series of SARS-CoV-2 main protease (M(pro)) inhibitors were designed and tested based on the active compound from high-throughput diverse compound library screens. The most efficacious compound (16b-3) displayed potent SARS-CoV-2 M(pro) inhibition with an IC(50) value of 116 nM and selectivity against SARS-CoV-2 M(pro) when compared to PL(pro) and RdRp. This new class of compounds could be used as potential leads for further optimization in anti COVID-19 drug discovery. Elsevier Ltd. 2022-02-15 2022-01-05 /pmc/articles/PMC8730469/ /pubmed/34998903 http://dx.doi.org/10.1016/j.bmcl.2022.128526 Text en © 2022 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
Chen, Weixiong
Feng, Bo
Han, Sheng
Wang, Peipei
Chen, Wuhong
Zang, Yi
Li, Jia
Hu, Youhong
Discovery of highly potent SARS-CoV-2 M(pro) inhibitors based on benzoisothiazolone scaffold
title Discovery of highly potent SARS-CoV-2 M(pro) inhibitors based on benzoisothiazolone scaffold
title_full Discovery of highly potent SARS-CoV-2 M(pro) inhibitors based on benzoisothiazolone scaffold
title_fullStr Discovery of highly potent SARS-CoV-2 M(pro) inhibitors based on benzoisothiazolone scaffold
title_full_unstemmed Discovery of highly potent SARS-CoV-2 M(pro) inhibitors based on benzoisothiazolone scaffold
title_short Discovery of highly potent SARS-CoV-2 M(pro) inhibitors based on benzoisothiazolone scaffold
title_sort discovery of highly potent sars-cov-2 m(pro) inhibitors based on benzoisothiazolone scaffold
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8730469/
https://www.ncbi.nlm.nih.gov/pubmed/34998903
http://dx.doi.org/10.1016/j.bmcl.2022.128526
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