The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b
Journal
Pharmaceutics
Journal Volume
14
Journal Issue
7
Date Issued
2022-07-21
Author(s)
Lee, Yue-Zhi
Hsu, Hsing-Yu
Yang, Cheng-Wei
Lin, Yi-Ling
Yang, Ruey-Bing
Liang, Jian-Jong
Liao, Chun-Che
Kao, Han-Chieh
Chang, Jang-Yang
Sytwu, Huey-Kang
Chen, Chiung-Tong
Lee, Shiow-Ju
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.
Subjects
COVID-19; IL-6; IL-8; MCP-1; MCP-3; OC43; SARS-CoV-2; ciclesonide; cytokine; tylophorine
SDGs
Publisher
MDPI
Type
journal article