The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b

Yue Zhi Lee; Hsing Yu Hsu; Cheng Wei Yang; Yi Ling Lin; Sui Yuan Chang; Ruey Bing Yang; Jian Jong Liang; Tai Ling Chao; Chun Che Liao; Han Chieh Kao; Jang Yang Chang; Huey Kang Sytwu; Chiung Tong Chen; Shiow Ju Lee

doi:10.3390/pharmaceutics14071511

The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b

Yue Zhi Lee, Hsing Yu Hsu, Cheng Wei Yang, Yi Ling Lin, Sui Yuan Chang, Ruey Bing Yang, Jian Jong Liang, Tai Ling Chao, Chun Che Liao, Han Chieh Kao, Jang Yang Chang, Huey Kang Sytwu, Chiung Tong Chen, Shiow Ju Lee

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

Ciclesonide 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.

Original language	English
Article number	1511
Journal	Pharmaceutics
Volume	14
Issue number	7
DOIs	https://doi.org/10.3390/pharmaceutics14071511
Publication status	Published - Jul 2022
Externally published	Yes

Keywords

ciclesonide
COVID-19
cytokine
IL-6
IL-8
MCP-1
MCP-3
OC43
SARS-CoV-2
tylophorine

ASJC Scopus subject areas

Pharmaceutical Science

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10.3390/pharmaceutics14071511

Cite this

Lee, Y. Z., Hsu, H. Y., Yang, C. W., Lin, Y. L., Chang, S. Y., Yang, R. B., Liang, J. J., Chao, T. L., Liao, C. C., Kao, H. C., Chang, J. Y., Sytwu, H. K., Chen, C. T., & Lee, S. J. (2022). The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b. Pharmaceutics, 14(7), Article 1511. https://doi.org/10.3390/pharmaceutics14071511

Lee, YZ, Hsu, HY, Yang, CW, Lin, YL, Chang, SY, Yang, RB, Liang, JJ, Chao, TL, Liao, CC, Kao, HC, Chang, JY, Sytwu, HK, Chen, CT & Lee, SJ 2022, 'The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b', Pharmaceutics, vol. 14, no. 7, 1511. https://doi.org/10.3390/pharmaceutics14071511

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title = "The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b",

abstract = "Ciclesonide 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.",

keywords = "ciclesonide, COVID-19, cytokine, IL-6, IL-8, MCP-1, MCP-3, OC43, SARS-CoV-2, tylophorine",

author = "Lee, {Yue Zhi} and Hsu, {Hsing Yu} and Yang, {Cheng Wei} 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 Chang, {Jang Yang} and Sytwu, {Huey Kang} and Chen, {Chiung Tong} and Lee, {Shiow Ju}",

note = "Funding Information: This work was funded by the National Health Research Institutes, Taiwan; Academia Sinica (AS-CFII-108-102); the Ministry of Science and Technology, Taiwan, (MOST 109-2327-B-400-003; MOST 109-3114-Y-001-001; MOST 109-2811-B-400-518; MOST 109-2327-B-002-009; MOST 110-2811-B-400-522); and the Ministry of Health and Welfare, Taiwan, for an emergent grant of COVID-19. Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = jul,

doi = "10.3390/pharmaceutics14071511",

language = "English",

volume = "14",

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AU - Lee, Yue Zhi

AU - Hsu, Hsing Yu

AU - Yang, Cheng Wei

AU - Lin, Yi Ling

AU - Chang, Sui Yuan

AU - Yang, Ruey Bing

AU - Liang, Jian Jong

AU - Chao, Tai Ling

AU - Liao, Chun Che

AU - Kao, Han Chieh

AU - Chang, Jang Yang

AU - Sytwu, Huey Kang

AU - Chen, Chiung Tong

AU - Lee, Shiow Ju

N1 - Funding Information: This work was funded by the National Health Research Institutes, Taiwan; Academia Sinica (AS-CFII-108-102); the Ministry of Science and Technology, Taiwan, (MOST 109-2327-B-400-003; MOST 109-3114-Y-001-001; MOST 109-2811-B-400-518; MOST 109-2327-B-002-009; MOST 110-2811-B-400-522); and the Ministry of Health and Welfare, Taiwan, for an emergent grant of COVID-19. Publisher Copyright: © 2022 by the authors.

PY - 2022/7

Y1 - 2022/7

N2 - Ciclesonide 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.

AB - Ciclesonide 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.

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KW - cytokine

KW - IL-6

KW - IL-8

KW - MCP-1

KW - MCP-3

KW - OC43

KW - SARS-CoV-2

KW - tylophorine

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M3 - Article

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VL - 14

JO - Pharmaceutics

JF - Pharmaceutics

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M1 - 1511

ER -

The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b

Abstract

Keywords

ASJC Scopus subject areas

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