tetano
Editor, Senior Moderator
Bioorg Med Chem Lett
. 2021 Apr 19;128052.
doi: 10.1016/j.bmcl.2021.128052. Online ahead of print.
Development of ciclesonide analogues that block SARS-CoV-2 RNA replication
Genichiro Tsuji[SUP] 1 [/SUP], Kenzo Yonemitsu[SUP] 2 [/SUP], Takahito Ito[SUP] 1 [/SUP], Yuta Yanase[SUP] 3 [/SUP], Masashi Uema[SUP] 2 [/SUP], Nobumichi Ohoka[SUP] 4 [/SUP], Takao Inoue[SUP] 4 [/SUP], Hiroshi Asakura[SUP] 2 [/SUP], Yosuke Demizu[SUP] 5 [/SUP]
Affiliations
Abstract
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.
Keywords: COVID-19; SARS-CoV-2; ciclesonide; endonuclease; viral growth inhibition.
. 2021 Apr 19;128052.
doi: 10.1016/j.bmcl.2021.128052. Online ahead of print.
Development of ciclesonide analogues that block SARS-CoV-2 RNA replication
Genichiro Tsuji[SUP] 1 [/SUP], Kenzo Yonemitsu[SUP] 2 [/SUP], Takahito Ito[SUP] 1 [/SUP], Yuta Yanase[SUP] 3 [/SUP], Masashi Uema[SUP] 2 [/SUP], Nobumichi Ohoka[SUP] 4 [/SUP], Takao Inoue[SUP] 4 [/SUP], Hiroshi Asakura[SUP] 2 [/SUP], Yosuke Demizu[SUP] 5 [/SUP]
Affiliations
- PMID: 33887440
- DOI: 10.1016/j.bmcl.2021.128052
Abstract
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.
Keywords: COVID-19; SARS-CoV-2; ciclesonide; endonuclease; viral growth inhibition.