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

• Main Authors: Yue-Zhi Lee (Author), Hsing-Yu Hsu (Author), Cheng-Wei Yang (Author), Yi-Ling Lin (Author), Sui-Yuan Chang (Author), Ruey-Bing Yang (Author), Jian-Jong Liang (Author), Tai-Ling Chao (Author), Chun-Che Liao (Author), Han-Chieh Kao (Author), Jang-Yang Chang (Author), Huey-Kang Sytwu (Author), Chiung-Tong Chen (Author), Shiow-Ju Lee (Author)
• Format: Book
• Published: MDPI AG, 2022-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

10.3390/pharmaceutics14071511
1999-4923