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Repurposing Niclosamide as a Novel Anti-SARS-CoV-2 Drug by Restricting Entry Protein CD147

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the global coronavirus disease 2019 (COVID-19) pandemic, and the search for effective treatments has been limited. Furthermore, the rapid mutations of SARS-CoV-2 have posed challenges to existing vaccines and neu...

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Autores principales: Yang, Zhe, Zhang, Qi, Wu, Xiaoqing, Hao, Siyuan, Hao, Xinbao, Jones, Elizabeth, Zhang, Yuxia, Qiu, Jianming, Xu, Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377517/
https://www.ncbi.nlm.nih.gov/pubmed/37509657
http://dx.doi.org/10.3390/biomedicines11072019
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author Yang, Zhe
Zhang, Qi
Wu, Xiaoqing
Hao, Siyuan
Hao, Xinbao
Jones, Elizabeth
Zhang, Yuxia
Qiu, Jianming
Xu, Liang
author_facet Yang, Zhe
Zhang, Qi
Wu, Xiaoqing
Hao, Siyuan
Hao, Xinbao
Jones, Elizabeth
Zhang, Yuxia
Qiu, Jianming
Xu, Liang
author_sort Yang, Zhe
collection PubMed
description The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the global coronavirus disease 2019 (COVID-19) pandemic, and the search for effective treatments has been limited. Furthermore, the rapid mutations of SARS-CoV-2 have posed challenges to existing vaccines and neutralizing antibodies, as they struggle to keep up with the increased viral transmissibility and immune evasion. However, there is hope in targeting the CD147-spike protein, which serves as an alternative point for the entry of SARS-CoV-2 into host cells. This protein has emerged as a promising therapeutic target for the development of drugs against COVID-19. Here, we demonstrate that the RNA-binding protein Human-antigen R (HuR) plays a crucial role in the post-transcriptional regulation of CD147 by directly binding to its 3′-untranslated region (UTR). We observed a decrease in CD147 levels across multiple cell lines upon HuR depletion. Furthermore, we identified that niclosamide can reduce CD147 by lowering the cytoplasmic translocation of HuR and reducing CD147 glycosylation. Moreover, our investigation revealed that SARS-CoV-2 infection induces an upregulation of CD147 in ACE2-expressing A549 cells, which can be effectively neutralized by niclosamide in a dose-dependent manner. Overall, our study unveils a novel regulatory mechanism of regulating CD147 through HuR and suggests niclosamide as a promising therapeutic option against COVID-19.
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spelling pubmed-103775172023-07-29 Repurposing Niclosamide as a Novel Anti-SARS-CoV-2 Drug by Restricting Entry Protein CD147 Yang, Zhe Zhang, Qi Wu, Xiaoqing Hao, Siyuan Hao, Xinbao Jones, Elizabeth Zhang, Yuxia Qiu, Jianming Xu, Liang Biomedicines Article The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the global coronavirus disease 2019 (COVID-19) pandemic, and the search for effective treatments has been limited. Furthermore, the rapid mutations of SARS-CoV-2 have posed challenges to existing vaccines and neutralizing antibodies, as they struggle to keep up with the increased viral transmissibility and immune evasion. However, there is hope in targeting the CD147-spike protein, which serves as an alternative point for the entry of SARS-CoV-2 into host cells. This protein has emerged as a promising therapeutic target for the development of drugs against COVID-19. Here, we demonstrate that the RNA-binding protein Human-antigen R (HuR) plays a crucial role in the post-transcriptional regulation of CD147 by directly binding to its 3′-untranslated region (UTR). We observed a decrease in CD147 levels across multiple cell lines upon HuR depletion. Furthermore, we identified that niclosamide can reduce CD147 by lowering the cytoplasmic translocation of HuR and reducing CD147 glycosylation. Moreover, our investigation revealed that SARS-CoV-2 infection induces an upregulation of CD147 in ACE2-expressing A549 cells, which can be effectively neutralized by niclosamide in a dose-dependent manner. Overall, our study unveils a novel regulatory mechanism of regulating CD147 through HuR and suggests niclosamide as a promising therapeutic option against COVID-19. MDPI 2023-07-18 /pmc/articles/PMC10377517/ /pubmed/37509657 http://dx.doi.org/10.3390/biomedicines11072019 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yang, Zhe
Zhang, Qi
Wu, Xiaoqing
Hao, Siyuan
Hao, Xinbao
Jones, Elizabeth
Zhang, Yuxia
Qiu, Jianming
Xu, Liang
Repurposing Niclosamide as a Novel Anti-SARS-CoV-2 Drug by Restricting Entry Protein CD147
title Repurposing Niclosamide as a Novel Anti-SARS-CoV-2 Drug by Restricting Entry Protein CD147
title_full Repurposing Niclosamide as a Novel Anti-SARS-CoV-2 Drug by Restricting Entry Protein CD147
title_fullStr Repurposing Niclosamide as a Novel Anti-SARS-CoV-2 Drug by Restricting Entry Protein CD147
title_full_unstemmed Repurposing Niclosamide as a Novel Anti-SARS-CoV-2 Drug by Restricting Entry Protein CD147
title_short Repurposing Niclosamide as a Novel Anti-SARS-CoV-2 Drug by Restricting Entry Protein CD147
title_sort repurposing niclosamide as a novel anti-sars-cov-2 drug by restricting entry protein cd147
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377517/
https://www.ncbi.nlm.nih.gov/pubmed/37509657
http://dx.doi.org/10.3390/biomedicines11072019
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