Lee, Yue-ZhiYue-ZhiLeeHsu, Hsing-YuHsing-YuHsuYang, Cheng-WeiCheng-WeiYangLin, Yi-LingYi-LingLinSUI-YUAN CHANGYang, Ruey-BingRuey-BingYangLiang, Jian-JongJian-JongLiangTAI-LING CHAOLiao, Chun-CheChun-CheLiaoKao, Han-ChiehHan-ChiehKaoChang, Jang-YangJang-YangChangSytwu, Huey-KangHuey-KangSytwuChen, Chiung-TongChiung-TongChenLee, Shiow-JuShiow-JuLee2022-09-062022-09-062022-07-211999-4923https://scholars.lib.ntu.edu.tw/handle/123456789/618540Ciclesonide 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.enCOVID-19; IL-6; IL-8; MCP-1; MCP-3; OC43; SARS-CoV-2; ciclesonide; cytokine; tylophorine[SDGs]SDG3journal article10.3390/pharmaceutics14071511358904062-s2.0-85136376382WOS:000832463200001https://api.elsevier.com/content/abstract/scopus_id/85136376382