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Zinc supplement augments the suppressive effects of repurposed drugs of NF-kappa B inhibitor on ACE2 expression in human lung cell lines in vitro

Ming-Cheng Lee, Yin-Kai Chen, Yih-Jen Hsu, Bor-Ru Lin
doi: https://doi.org/10.1101/2021.01.27.428372
Ming-Cheng Lee
1Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10051, Taiwan, R.O.C.
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Yin-Kai Chen
2Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 10002, Taiwan, R.O.C.
3Department of Hematology, National Taiwan University Cancer Center, Taipei 10672, Taiwan, R.O.C.
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Yih-Jen Hsu
4Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital, Taipei 10051, Taiwan, R.O.C.
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Bor-Ru Lin
1Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10051, Taiwan, R.O.C.
4Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital, Taipei 10051, Taiwan, R.O.C.
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  • For correspondence: brucelin@ntuh.gov.tw
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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a vast number of infections and fatalities worldwide. As the development and safety validation of effective vaccines are ongoing, drug repurposing is most efficient approach to search FDA approved agents against coronavirus disease 2019 (COVID-19). In the present study, we found that endogenous ACE2 expressions could be detected in H322M and Calu-3 cell lines, as well as their ACE2 mRNA and protein expressions were suppressed by pyrrolidine dithiocarbamate (PDTC), a NF-kappa B inhibitor, in dose- and time-dependent manners. Moreover, N-acetyl-cysteine (NAC) pretreatment reversed PDTC-induced ACE2 suppression, as well as the combined treatment of hydrogen peroxide and knockdown of p50 subunit of NF-kappa B by siRNA reduced ACE2 expression in H322M cells. In addition, anthelmintic drug triclabendazole and antiprotozoal drug emetine, repurposed drugs of NF-kappa B inhibitor, also inhibited ACE2 mRNA and protein expressions in H322M cells. Moreover, zinc supplement augmented the suppressive effects of triclabendazole and emetine on ACE2 suppression in H322M and Calu-3 cells. Taken together, these results indicate that ACE2 expression is modulated by reactive oxygen species (ROS) and NF-kappa B signal in human lung cell lines, and zinc combination with triclabendazole or emetine has the clinical potential for the prevention and treatment of COVID-19.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 27, 2021.
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Zinc supplement augments the suppressive effects of repurposed drugs of NF-kappa B inhibitor on ACE2 expression in human lung cell lines in vitro
Ming-Cheng Lee, Yin-Kai Chen, Yih-Jen Hsu, Bor-Ru Lin
bioRxiv 2021.01.27.428372; doi: https://doi.org/10.1101/2021.01.27.428372
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Zinc supplement augments the suppressive effects of repurposed drugs of NF-kappa B inhibitor on ACE2 expression in human lung cell lines in vitro
Ming-Cheng Lee, Yin-Kai Chen, Yih-Jen Hsu, Bor-Ru Lin
bioRxiv 2021.01.27.428372; doi: https://doi.org/10.1101/2021.01.27.428372

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