Development of ciclesonide analogues that block SARS-CoV-2 RNA replication. (1st July 2021)

• Record Type: Journal Article
• Authors: Tsuji, Genichiro; Yonemitsu, Kenzo; Ito, Takahito; Yanase, Yuta; Uema, Masashi; Ohoka, Nobumichi; Inoue, Takao; Asakura, Hiroshi; Demizu, Yosuke
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 43(2021)
• Publication Date: 2021-07-01
• Subjects: SARS-CoV-2 -- COVID-19 -- Endonuclease -- Ciclesonide -- Viral growth inhibition; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2021.128052
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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.