| Autor: |
Jia Liu, Furun Wang, Xi Wang, Shiyong Fan, Yufeng Li, Mingyue Xu, Hengrui Hu, Ke Liu, Bohong Zheng, Lingchao Wang, Huanyu Zhang, Jiang Li, Wei Li, Wenpeng Zhang, Zhihong Hu, Ruiyuan Cao, Xiaomei Zhuang, Manli Wang, Wu Zhong |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
MedComm, Vol 4, Iss 1, Pp n/a-n/a (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2688-2663 |
| DOI: |
10.1002/mco2.206 |
| Popis: |
Abstract 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 (EC90) in human lungs. This study provides insights into the route‐dependent pulmonary biodistribution of TET associated with its efficacy. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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