@article{9d237fee73bf4300bc04d9dd30aaae5c,
title = "Remdesivir and Cyclosporine Synergistically Inhibit the Human Coronaviruses OC43 and SARS-CoV-2",
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.",
keywords = "COVID-19, cyclosporine, IL-6, IL-8, OC43, remdesivir, SARS-CoV-2, synergistic",
author = "Hsu, {Hsing Yu} and Yang, {Cheng Wei} and Lee, {Yue Zhi} and Lin, {Yi Ling} and Chang, {Sui Yuan} and Yang, {Ruey Bing} and Liang, {Jian Jong} and Chao, {Tai Ling} and Liao, {Chun Che} and Kao, {Han Chieh} and Wu, {Szu Huei} and Chang, {Jang Yang} and Sytwu, {Huey Kang} and Chen, {Chiung Tong} and Lee, {Shiow Ju}",
note = "Funding Information: The authors gratefully acknowledge Kung-Yee Liang, National Health Research Institutes, for his full support on this work. We also would like to acknowledge Taiwan CDC for providing SARS-CoV-2 TCDC#4 (hCoV-19/Taiwan/4/2020) and the services provided by the Biosafety Level-3 Laboratory of the First Core Laboratory, National Taiwan University College of Medicine and by IBMS P3 facility at Academia Sinica. Funding Information: This work was funded by the National Health Research Institutes, Taiwan, R.O.C.; Academia Sinica (AS-CFII-108-102); the Ministry of Science and Technology, Taiwan, R.O.C (MOST 109-2327-B-400-003; MOST 109-3114-Y-001-001; MOST 109-2811-B-400-518; MOST109-2327-B-002–009); and the Ministry of Health and Welfare, Taiwan, R.O.C. for an emergent grant of COVID-19. Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2021 Hsu, Yang, Lee, Lin, Chang, Yang, Liang, Chao, Liao, Kao, Wu, Chang, Sytwu, Chen and Lee.",
year = "2021",
month = aug,
day = "13",
doi = "10.3389/fphar.2021.706901",
language = "English",
volume = "12",
journal = "Frontiers in Pharmacology",
issn = "1663-9812",
publisher = "Frontiers Media SA",
}