Hsu, Hsing-YuHsing-YuHsuYang, Cheng-WeiCheng-WeiYangLee, Yue-ZhiYue-ZhiLeeLin, Yi-LingYi-LingLinSUI-YUAN CHANGYang, Ruey-BingRuey-BingYangLiang, Jian-JongJian-JongLiangTAI-LING CHAOLiao, Chun-CheChun-CheLiaoKao, Han-ChiehHan-ChiehKaoWu, Szu-HueiSzu-HueiWuChang, Jang-YangJang-YangChangSytwu, Huey-KangHuey-KangSytwuChen, Chiung-TongChiung-TongChenLee, Shiow-JuShiow-JuLee2021-11-072021-11-0720211663-9812https://scholars.lib.ntu.edu.tw/handle/123456789/586531Remdesivir, a prodrug targeting RNA-dependent-RNA-polymerase, and cyclosporine, a calcineurin inhibitor, individually exerted inhibitory activity against human coronavirus OC43 (HCoV-OC43) in HCT-8 and MRC-5 cells at EC50 values of 96 ± 34 ∼ 85 ± 23 nM and 2,920 ± 364 ∼ 4,419 ± 490 nM, respectively. When combined, these two drugs synergistically inhibited HCoV-OC43 in both HCT-8 and MRC-5 cells assayed by immunofluorescence assay (IFA). Remdesivir and cyclosporine also separately reduced IL-6 production induced by HCoV-OC43 in human lung fibroblasts MRC-5 cells with EC50 values of 224 ± 53 nM and 1,292 ± 352 nM, respectively; and synergistically reduced it when combined. Similar trends were observed for SARS-CoV-2, which were 1) separately inhibited by remdesivir and cyclosporine with respective EC50 values of 3,962 ± 303 nM and 7,213 ± 143 nM by IFA, and 291 ± 91 nM and 6,767 ± 1,827 nM by a plaque-formation assay; and 2) synergistically inhibited by their combination, again by IFA and plaque-formation assay. Collectively, these results suggest that the combination of remdesivir and cyclosporine merits further study as a possible treatment for COVID-19 complexed with a cytokine storm.enCOVID-19; IL-6; IL-8; OC43; SARS-CoV-2; cyclosporine; remdesivir; synergistic[SDGs]SDG3cyclosporine; interleukin 6; remdesivir; Article; controlled study; coronavirus disease 2019; cytokine production; cytokine storm; drug inhibition; EC50; HCT 8 cell line; human; human cell; Human coronavirus OC43; immunofluorescence assay; lung fibroblast; MRC-5 cell line; nonhuman; plaque forming cell assay; Severe acute respiratory syndrome coronavirus 2; synergistic effect; Vero C1008 cell line; Western blottingjournal article10.3389/fphar.2021.706901344839142-s2.0-85114176838https://scholars.lib.ntu.edu.tw/handle/123456789/582779