Remdesivir and Cyclosporine Synergistically Inhibit the Human Coronaviruses OC43 and SARS-CoV-2
Journal
Frontiers in pharmacology
Journal Volume
12
Date Issued
2021
Author(s)
Hsu, Hsing-Yu
Yang, Cheng-Wei
Lee, Yue-Zhi
Lin, Yi-Ling
Yang, Ruey-Bing
Liang, Jian-Jong
Liao, Chun-Che
Kao, Han-Chieh
Wu, Szu-Huei
Chang, Jang-Yang
Sytwu, Huey-Kang
Chen, Chiung-Tong
Lee, Shiow-Ju
Abstract
Remdesivir, 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.
Subjects
COVID-19; IL-6; IL-8; OC43; SARS-CoV-2; cyclosporine; remdesivir; synergistic
SDGs
Other Subjects
cyclosporine; 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 blotting
Type
journal article