The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b

Yue Zhi Lee, Hsing Yu Hsu, Cheng Wei Yang, Yi Ling Lin, Sui Yuan Chang, Ruey Bing Yang, Jian Jong Liang, Tai Ling Chao, Chun Che Liao, Han Chieh Kao, Jang Yang Chang, Huey Kang Sytwu, Chiung Tong Chen, Shiow Ju Lee

Research output: Contribution to journalArticlepeer-review

Abstract

Ciclesonide is an inhaled corticosteroid used to treat asthma and has been repurposed as a treatment for mildly ill COVID-19 patients, but its precise mechanism of action is unclear. Herein, we report that ciclesonide blocks the coronavirus-induced production of the cytokines IL-6, IL-8, and MCP-1 by increasing IκBα protein levels and significantly decreasing p65 nuclear translocation. Furthermore, we found that the combination of ciclesonide and dbq33b, a potent tylophorine-based coronavirus inhibitor that affects coronavirus-induced NF-κB activation a little, additively and synergistically decreased coronavirus-induced IL-6, IL-8, and MCP-1 cytokine levels, and synergistically inhibited the replication of both HCoV-OC43 and SARS-CoV-2. Collectively, the combination of ciclesonide and dbq33b merits consideration as a treatment for COVID-19 patients who may otherwise be overwhelmed by high viral loads and an NF-κB-mediated cytokine storm.

Original languageEnglish
Article number1511
JournalPharmaceutics
Volume14
Issue number7
DOIs
Publication statusPublished - Jul 2022
Externally publishedYes

Keywords

  • ciclesonide
  • COVID-19
  • cytokine
  • IL-6
  • IL-8
  • MCP-1
  • MCP-3
  • OC43
  • SARS-CoV-2
  • tylophorine

ASJC Scopus subject areas

  • Pharmaceutical Science

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