Cargando…

Remdesivir and Cyclosporine Synergistically Inhibit the Human Coronaviruses OC43 and SARS-CoV-2

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 EC(50) values of 96 ± 34 ∼ 85 ± 23 nM and 2,920 ± 364 ∼ 4,419 ± 490 nM, respectivel...

Descripción completa

Detalles Bibliográficos
Autores principales: Hsu, Hsing-Yu, Yang, Cheng-Wei, Lee, Yue-Zhi, Lin, Yi-Ling, Chang, Sui-Yuan, Yang, Ruey-Bing, Liang, Jian-Jong, Chao, Tai-Ling, Liao, Chun-Che, Kao, Han-Chieh, Wu, Szu-Huei, Chang, Jang-Yang, Sytwu, Huey-Kang, Chen, Chiung-Tong, Lee, Shiow-Ju
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409573/
https://www.ncbi.nlm.nih.gov/pubmed/34483914
http://dx.doi.org/10.3389/fphar.2021.706901
_version_ 1783747010906554368
author Hsu, Hsing-Yu
Yang, Cheng-Wei
Lee, Yue-Zhi
Lin, Yi-Ling
Chang, Sui-Yuan
Yang, Ruey-Bing
Liang, Jian-Jong
Chao, Tai-Ling
Liao, Chun-Che
Kao, Han-Chieh
Wu, Szu-Huei
Chang, Jang-Yang
Sytwu, Huey-Kang
Chen, Chiung-Tong
Lee, Shiow-Ju
author_facet Hsu, Hsing-Yu
Yang, Cheng-Wei
Lee, Yue-Zhi
Lin, Yi-Ling
Chang, Sui-Yuan
Yang, Ruey-Bing
Liang, Jian-Jong
Chao, Tai-Ling
Liao, Chun-Che
Kao, Han-Chieh
Wu, Szu-Huei
Chang, Jang-Yang
Sytwu, Huey-Kang
Chen, Chiung-Tong
Lee, Shiow-Ju
author_sort Hsu, Hsing-Yu
collection PubMed
description 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 EC(50) 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 EC(50) 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 EC(50) 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.
format Online
Article
Text
id pubmed-8409573
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-84095732021-09-02 Remdesivir and Cyclosporine Synergistically Inhibit the Human Coronaviruses OC43 and SARS-CoV-2 Hsu, Hsing-Yu Yang, Cheng-Wei Lee, Yue-Zhi Lin, Yi-Ling Chang, Sui-Yuan Yang, Ruey-Bing Liang, Jian-Jong Chao, Tai-Ling Liao, Chun-Che Kao, Han-Chieh Wu, Szu-Huei Chang, Jang-Yang Sytwu, Huey-Kang Chen, Chiung-Tong Lee, Shiow-Ju Front Pharmacol Pharmacology 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 EC(50) 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 EC(50) 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 EC(50) 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. Frontiers Media S.A. 2021-08-13 /pmc/articles/PMC8409573/ /pubmed/34483914 http://dx.doi.org/10.3389/fphar.2021.706901 Text en Copyright © 2021 Hsu, Yang, Lee, Lin, Chang, Yang, Liang, Chao, Liao, Kao, Wu, Chang, Sytwu, Chen and Lee. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Hsu, Hsing-Yu
Yang, Cheng-Wei
Lee, Yue-Zhi
Lin, Yi-Ling
Chang, Sui-Yuan
Yang, Ruey-Bing
Liang, Jian-Jong
Chao, Tai-Ling
Liao, Chun-Che
Kao, Han-Chieh
Wu, Szu-Huei
Chang, Jang-Yang
Sytwu, Huey-Kang
Chen, Chiung-Tong
Lee, Shiow-Ju
Remdesivir and Cyclosporine Synergistically Inhibit the Human Coronaviruses OC43 and SARS-CoV-2
title Remdesivir and Cyclosporine Synergistically Inhibit the Human Coronaviruses OC43 and SARS-CoV-2
title_full Remdesivir and Cyclosporine Synergistically Inhibit the Human Coronaviruses OC43 and SARS-CoV-2
title_fullStr Remdesivir and Cyclosporine Synergistically Inhibit the Human Coronaviruses OC43 and SARS-CoV-2
title_full_unstemmed Remdesivir and Cyclosporine Synergistically Inhibit the Human Coronaviruses OC43 and SARS-CoV-2
title_short Remdesivir and Cyclosporine Synergistically Inhibit the Human Coronaviruses OC43 and SARS-CoV-2
title_sort remdesivir and cyclosporine synergistically inhibit the human coronaviruses oc43 and sars-cov-2
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409573/
https://www.ncbi.nlm.nih.gov/pubmed/34483914
http://dx.doi.org/10.3389/fphar.2021.706901
work_keys_str_mv AT hsuhsingyu remdesivirandcyclosporinesynergisticallyinhibitthehumancoronavirusesoc43andsarscov2
AT yangchengwei remdesivirandcyclosporinesynergisticallyinhibitthehumancoronavirusesoc43andsarscov2
AT leeyuezhi remdesivirandcyclosporinesynergisticallyinhibitthehumancoronavirusesoc43andsarscov2
AT linyiling remdesivirandcyclosporinesynergisticallyinhibitthehumancoronavirusesoc43andsarscov2
AT changsuiyuan remdesivirandcyclosporinesynergisticallyinhibitthehumancoronavirusesoc43andsarscov2
AT yangrueybing remdesivirandcyclosporinesynergisticallyinhibitthehumancoronavirusesoc43andsarscov2
AT liangjianjong remdesivirandcyclosporinesynergisticallyinhibitthehumancoronavirusesoc43andsarscov2
AT chaotailing remdesivirandcyclosporinesynergisticallyinhibitthehumancoronavirusesoc43andsarscov2
AT liaochunche remdesivirandcyclosporinesynergisticallyinhibitthehumancoronavirusesoc43andsarscov2
AT kaohanchieh remdesivirandcyclosporinesynergisticallyinhibitthehumancoronavirusesoc43andsarscov2
AT wuszuhuei remdesivirandcyclosporinesynergisticallyinhibitthehumancoronavirusesoc43andsarscov2
AT changjangyang remdesivirandcyclosporinesynergisticallyinhibitthehumancoronavirusesoc43andsarscov2
AT sytwuhueykang remdesivirandcyclosporinesynergisticallyinhibitthehumancoronavirusesoc43andsarscov2
AT chenchiungtong remdesivirandcyclosporinesynergisticallyinhibitthehumancoronavirusesoc43andsarscov2
AT leeshiowju remdesivirandcyclosporinesynergisticallyinhibitthehumancoronavirusesoc43andsarscov2