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Antiviral effects and tissue exposure of tetrandrine against SARS‐CoV‐2 infection and COVID‐19

Tetrandrine (TET) has been used to treat silicosis in China for decades. The aim of this study was to facilitate rational repurposing of TET against SARS‐CoV‐2 infection. In this study, we confirmed that TET exhibited antiviral potency against SARS‐CoV‐2 in the African green monkey kidney (Vero E6),...

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Autores principales: Liu, Jia, Wang, Furun, Wang, Xi, Fan, Shiyong, Li, Yufeng, Xu, Mingyue, Hu, Hengrui, Liu, Ke, Zheng, Bohong, Wang, Lingchao, Zhang, Huanyu, Li, Jiang, Li, Wei, Zhang, Wenpeng, Hu, Zhihong, Cao, Ruiyuan, Zhuang, Xiaomei, Wang, Manli, Zhong, Wu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9851407/
https://www.ncbi.nlm.nih.gov/pubmed/36699286
http://dx.doi.org/10.1002/mco2.206
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author Liu, Jia
Wang, Furun
Wang, Xi
Fan, Shiyong
Li, Yufeng
Xu, Mingyue
Hu, Hengrui
Liu, Ke
Zheng, Bohong
Wang, Lingchao
Zhang, Huanyu
Li, Jiang
Li, Wei
Zhang, Wenpeng
Hu, Zhihong
Cao, Ruiyuan
Zhuang, Xiaomei
Wang, Manli
Zhong, Wu
author_facet Liu, Jia
Wang, Furun
Wang, Xi
Fan, Shiyong
Li, Yufeng
Xu, Mingyue
Hu, Hengrui
Liu, Ke
Zheng, Bohong
Wang, Lingchao
Zhang, Huanyu
Li, Jiang
Li, Wei
Zhang, Wenpeng
Hu, Zhihong
Cao, Ruiyuan
Zhuang, Xiaomei
Wang, Manli
Zhong, Wu
author_sort Liu, Jia
collection PubMed
description Tetrandrine (TET) has been used to treat silicosis in China for decades. The aim of this study was to facilitate rational repurposing of TET against SARS‐CoV‐2 infection. In this study, we confirmed that TET exhibited antiviral potency against SARS‐CoV‐2 in the African green monkey kidney (Vero E6), human hepatocarcinoma (Huh7), and human lung adenocarcinoma epithelial (Calu‐3) cell lines. TET functioned during the early‐entry stage of SARS‐CoV‐2 and impeded intracellular trafficking of the virus from early endosomes to endolysosomes. An in vivo study that used adenovirus (AdV) 5‐human angiotensin‐converting enzyme 2 (hACE2)‐transduced mice showed that although TET did not reduce pulmonary viral load, it significantly alleviated pathological damage in SARS‐CoV‐2‐infected murine lungs. The systemic preclinical pharmacokinetics were investigated based on in vivo and in vitro models, and the route‐dependent biodistribution of TET was explored. TET had a large volume of distribution, which contributed to its high tissue accumulation. Inhaled administration helped TET target the lung and reduced its exposure to other tissues, which mitigated its off‐target toxicity. Based on the available human pharmacokinetic data, it appeared feasible to achieve an unbound TET 90% maximal effective concentration (EC(90)) in human lungs. This study provides insights into the route‐dependent pulmonary biodistribution of TET associated with its efficacy.
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spelling pubmed-98514072023-01-24 Antiviral effects and tissue exposure of tetrandrine against SARS‐CoV‐2 infection and COVID‐19 Liu, Jia Wang, Furun Wang, Xi Fan, Shiyong Li, Yufeng Xu, Mingyue Hu, Hengrui Liu, Ke Zheng, Bohong Wang, Lingchao Zhang, Huanyu Li, Jiang Li, Wei Zhang, Wenpeng Hu, Zhihong Cao, Ruiyuan Zhuang, Xiaomei Wang, Manli Zhong, Wu MedComm (2020) Original Articles Tetrandrine (TET) has been used to treat silicosis in China for decades. The aim of this study was to facilitate rational repurposing of TET against SARS‐CoV‐2 infection. In this study, we confirmed that TET exhibited antiviral potency against SARS‐CoV‐2 in the African green monkey kidney (Vero E6), human hepatocarcinoma (Huh7), and human lung adenocarcinoma epithelial (Calu‐3) cell lines. TET functioned during the early‐entry stage of SARS‐CoV‐2 and impeded intracellular trafficking of the virus from early endosomes to endolysosomes. An in vivo study that used adenovirus (AdV) 5‐human angiotensin‐converting enzyme 2 (hACE2)‐transduced mice showed that although TET did not reduce pulmonary viral load, it significantly alleviated pathological damage in SARS‐CoV‐2‐infected murine lungs. The systemic preclinical pharmacokinetics were investigated based on in vivo and in vitro models, and the route‐dependent biodistribution of TET was explored. TET had a large volume of distribution, which contributed to its high tissue accumulation. Inhaled administration helped TET target the lung and reduced its exposure to other tissues, which mitigated its off‐target toxicity. Based on the available human pharmacokinetic data, it appeared feasible to achieve an unbound TET 90% maximal effective concentration (EC(90)) in human lungs. This study provides insights into the route‐dependent pulmonary biodistribution of TET associated with its efficacy. John Wiley and Sons Inc. 2023-01-19 /pmc/articles/PMC9851407/ /pubmed/36699286 http://dx.doi.org/10.1002/mco2.206 Text en © 2023 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Liu, Jia
Wang, Furun
Wang, Xi
Fan, Shiyong
Li, Yufeng
Xu, Mingyue
Hu, Hengrui
Liu, Ke
Zheng, Bohong
Wang, Lingchao
Zhang, Huanyu
Li, Jiang
Li, Wei
Zhang, Wenpeng
Hu, Zhihong
Cao, Ruiyuan
Zhuang, Xiaomei
Wang, Manli
Zhong, Wu
Antiviral effects and tissue exposure of tetrandrine against SARS‐CoV‐2 infection and COVID‐19
title Antiviral effects and tissue exposure of tetrandrine against SARS‐CoV‐2 infection and COVID‐19
title_full Antiviral effects and tissue exposure of tetrandrine against SARS‐CoV‐2 infection and COVID‐19
title_fullStr Antiviral effects and tissue exposure of tetrandrine against SARS‐CoV‐2 infection and COVID‐19
title_full_unstemmed Antiviral effects and tissue exposure of tetrandrine against SARS‐CoV‐2 infection and COVID‐19
title_short Antiviral effects and tissue exposure of tetrandrine against SARS‐CoV‐2 infection and COVID‐19
title_sort antiviral effects and tissue exposure of tetrandrine against sars‐cov‐2 infection and covid‐19
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9851407/
https://www.ncbi.nlm.nih.gov/pubmed/36699286
http://dx.doi.org/10.1002/mco2.206
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