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Azelnidipine Exhibits In Vitro and In Vivo Antiviral Effects against Flavivirus Infections by Targeting the Viral RdRp
Flaviviruses, represented by Zika and dengue virus (ZIKV and DENV), are widely present around the world and cause various diseases with serious consequences. However, no antiviral drugs have been clinically approved for use against them. Azelnidipine (ALP) is a dihydropyridine calcium channel blocke...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230735/ https://www.ncbi.nlm.nih.gov/pubmed/35746699 http://dx.doi.org/10.3390/v14061228 |
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author | Wang, Zhuang Yan, Yunzheng Dai, Qingsong Xu, Yijie Yin, Jiye Li, Wei Li, Yuexiang Yang, Xiaotong Guo, Xiaojia Liu, Miaomiao Chen, Xingjuan Cao, Ruiyuan Zhong, Wu |
author_facet | Wang, Zhuang Yan, Yunzheng Dai, Qingsong Xu, Yijie Yin, Jiye Li, Wei Li, Yuexiang Yang, Xiaotong Guo, Xiaojia Liu, Miaomiao Chen, Xingjuan Cao, Ruiyuan Zhong, Wu |
author_sort | Wang, Zhuang |
collection | PubMed |
description | Flaviviruses, represented by Zika and dengue virus (ZIKV and DENV), are widely present around the world and cause various diseases with serious consequences. However, no antiviral drugs have been clinically approved for use against them. Azelnidipine (ALP) is a dihydropyridine calcium channel blocker and has been approved for use as an antihypertensive drug. In the present study, ALP was found to show potent anti-flavivirus activities in vitro and in vivo. ALP effectively prevented the cytopathic effect induced by ZIKV and DENV and inhibited the production of viral RNA and viral protein in a dose-dependent manner. Moreover, treatment with 0.3 mg/kg of ALP protected 88.89% of mice from lethal challenge. Furthermore, using the time-of-drug-addition assay, the enzymatic inhibition assay, the molecular docking, and the surface plasmon resonance assay, we revealed that ALP acted at the replication stage of the viral infection cycle by targeting the viral RNA-dependent RNA polymerase. These findings highlight the potential for the use of ALP as an antiviral agent to combat flavivirus infections. |
format | Online Article Text |
id | pubmed-9230735 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92307352022-06-25 Azelnidipine Exhibits In Vitro and In Vivo Antiviral Effects against Flavivirus Infections by Targeting the Viral RdRp Wang, Zhuang Yan, Yunzheng Dai, Qingsong Xu, Yijie Yin, Jiye Li, Wei Li, Yuexiang Yang, Xiaotong Guo, Xiaojia Liu, Miaomiao Chen, Xingjuan Cao, Ruiyuan Zhong, Wu Viruses Article Flaviviruses, represented by Zika and dengue virus (ZIKV and DENV), are widely present around the world and cause various diseases with serious consequences. However, no antiviral drugs have been clinically approved for use against them. Azelnidipine (ALP) is a dihydropyridine calcium channel blocker and has been approved for use as an antihypertensive drug. In the present study, ALP was found to show potent anti-flavivirus activities in vitro and in vivo. ALP effectively prevented the cytopathic effect induced by ZIKV and DENV and inhibited the production of viral RNA and viral protein in a dose-dependent manner. Moreover, treatment with 0.3 mg/kg of ALP protected 88.89% of mice from lethal challenge. Furthermore, using the time-of-drug-addition assay, the enzymatic inhibition assay, the molecular docking, and the surface plasmon resonance assay, we revealed that ALP acted at the replication stage of the viral infection cycle by targeting the viral RNA-dependent RNA polymerase. These findings highlight the potential for the use of ALP as an antiviral agent to combat flavivirus infections. MDPI 2022-06-05 /pmc/articles/PMC9230735/ /pubmed/35746699 http://dx.doi.org/10.3390/v14061228 Text en © 2022 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 Wang, Zhuang Yan, Yunzheng Dai, Qingsong Xu, Yijie Yin, Jiye Li, Wei Li, Yuexiang Yang, Xiaotong Guo, Xiaojia Liu, Miaomiao Chen, Xingjuan Cao, Ruiyuan Zhong, Wu Azelnidipine Exhibits In Vitro and In Vivo Antiviral Effects against Flavivirus Infections by Targeting the Viral RdRp |
title | Azelnidipine Exhibits In Vitro and In Vivo Antiviral Effects against Flavivirus Infections by Targeting the Viral RdRp |
title_full | Azelnidipine Exhibits In Vitro and In Vivo Antiviral Effects against Flavivirus Infections by Targeting the Viral RdRp |
title_fullStr | Azelnidipine Exhibits In Vitro and In Vivo Antiviral Effects against Flavivirus Infections by Targeting the Viral RdRp |
title_full_unstemmed | Azelnidipine Exhibits In Vitro and In Vivo Antiviral Effects against Flavivirus Infections by Targeting the Viral RdRp |
title_short | Azelnidipine Exhibits In Vitro and In Vivo Antiviral Effects against Flavivirus Infections by Targeting the Viral RdRp |
title_sort | azelnidipine exhibits in vitro and in vivo antiviral effects against flavivirus infections by targeting the viral rdrp |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230735/ https://www.ncbi.nlm.nih.gov/pubmed/35746699 http://dx.doi.org/10.3390/v14061228 |
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