Development of ciclesonide analogues that block SARS-CoV-2 RNA replication

Ciclesonide is an inhaled corticosteroid used to treat asthma and is currently undergoing clinical trials for treatment of coronavirus disease 2019 (COVID-19). An active metabolite of ciclesonide, Cic2, was recently reported to repress severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) gen...

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Autores principales: Tsuji, Genichiro, Yonemitsu, Kenzo, Ito, Takahito, Yanase, Yuta, Uema, Masashi, Ohoka, Nobumichi, Inoue, Takao, Asakura, Hiroshi, Demizu, Yosuke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055493/
https://www.ncbi.nlm.nih.gov/pubmed/33887440
http://dx.doi.org/10.1016/j.bmcl.2021.128052
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author Tsuji, Genichiro
Yonemitsu, Kenzo
Ito, Takahito
Yanase, Yuta
Uema, Masashi
Ohoka, Nobumichi
Inoue, Takao
Asakura, Hiroshi
Demizu, Yosuke
author_facet Tsuji, Genichiro
Yonemitsu, Kenzo
Ito, Takahito
Yanase, Yuta
Uema, Masashi
Ohoka, Nobumichi
Inoue, Takao
Asakura, Hiroshi
Demizu, Yosuke
author_sort Tsuji, Genichiro
collection PubMed
description Ciclesonide is an inhaled corticosteroid used to treat asthma and is currently undergoing clinical trials for treatment of coronavirus disease 2019 (COVID-19). An active metabolite of ciclesonide, Cic2, was recently reported to repress severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genomic RNA replication. Herein, we designed and synthesized a few types of ciclesonide analogues. Cic4 (bearing an azide group) and Cic6 (bearing a chloro group) potently decreased SARS-CoV-2 viral replication and had low cytotoxicity compared with Cic2 (bearing a hydroxy group). These compounds are promising as novel therapeutic agents for COVID-19 that show significant antiviral activity.
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spelling pubmed-80554932021-04-20 Development of ciclesonide analogues that block SARS-CoV-2 RNA replication Tsuji, Genichiro Yonemitsu, Kenzo Ito, Takahito Yanase, Yuta Uema, Masashi Ohoka, Nobumichi Inoue, Takao Asakura, Hiroshi Demizu, Yosuke Bioorg Med Chem Lett Article Ciclesonide is an inhaled corticosteroid used to treat asthma and is currently undergoing clinical trials for treatment of coronavirus disease 2019 (COVID-19). An active metabolite of ciclesonide, Cic2, was recently reported to repress severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genomic RNA replication. Herein, we designed and synthesized a few types of ciclesonide analogues. Cic4 (bearing an azide group) and Cic6 (bearing a chloro group) potently decreased SARS-CoV-2 viral replication and had low cytotoxicity compared with Cic2 (bearing a hydroxy group). These compounds are promising as novel therapeutic agents for COVID-19 that show significant antiviral activity. Elsevier Ltd. 2021-07-01 2021-04-20 /pmc/articles/PMC8055493/ /pubmed/33887440 http://dx.doi.org/10.1016/j.bmcl.2021.128052 Text en © 2021 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
Tsuji, Genichiro
Yonemitsu, Kenzo
Ito, Takahito
Yanase, Yuta
Uema, Masashi
Ohoka, Nobumichi
Inoue, Takao
Asakura, Hiroshi
Demizu, Yosuke
Development of ciclesonide analogues that block SARS-CoV-2 RNA replication
title Development of ciclesonide analogues that block SARS-CoV-2 RNA replication
title_full Development of ciclesonide analogues that block SARS-CoV-2 RNA replication
title_fullStr Development of ciclesonide analogues that block SARS-CoV-2 RNA replication
title_full_unstemmed Development of ciclesonide analogues that block SARS-CoV-2 RNA replication
title_short Development of ciclesonide analogues that block SARS-CoV-2 RNA replication
title_sort development of ciclesonide analogues that block sars-cov-2 rna replication
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055493/
https://www.ncbi.nlm.nih.gov/pubmed/33887440
http://dx.doi.org/10.1016/j.bmcl.2021.128052
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