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千金藤素对叙利亚仓鼠模型中SARS-CoV-2诱导疾病的药理作用。

Pharmacological effect of cepharanthine on SARS-CoV-2-induced disease in a Syrian hamster model.

作者信息

Uematsu Takayuki, Takai-Todaka Reiko, Haga Kei, Kobayashi Hideyuki, Imajima Makiko, Kobayashi Noritada, Katayama Kazuhiko, Hanaki Hideaki

机构信息

Biomedical Laboratory, Division of Biomedical Research, Kitasato University Medical Center, Arai, Kitamoto, Saitama, Japan.

Laboratory of Viral Infection Control, Ōmura Satoshi Memorial Institute, Kitasato University, Tokyo, Japan.

出版信息

J Infect Chemother. 2025 Jan;31(1):102505. doi: 10.1016/j.jiac.2024.08.020. Epub 2024 Aug 27.

DOI:10.1016/j.jiac.2024.08.020
PMID:39197667
Abstract

BACKGROUND

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global public health threat. Although several effective vaccines and therapeutics have been developed, continuous emergence of new variants necessitates development of drugs with different mechanisms of action. Recent studies indicate that cepharanthine, a chemical derivative purified from Stephania cepharantha, inhibits SARS-CoV-2 replication in vitro.

METHODS

This study examined the in vivo effects of cepharanthine using a Syrian hamster SARS-CoV-2 infection model. To evaluate the prophylactic and therapeutic effects, cepharanthine was intranasally administered before or after SARS-CoV-2 infection. Effects were assessed by monitoring body weight changes, lung pathology, lung viral load, and inflammatory response in the lungs.

RESULTS

Pre-infection administration of cepharanthine resulted in less weight loss, reduced virus titers, alleviated histopathological severity, and decreased lung inflammation. Furthermore, post-infection administration of cepharanthine also exhibited therapeutic effects.

CONCLUSIONS

This study demonstrated that both prophylactic and therapeutic administration of cepharanthine reduces the pathogenesis of COVID-19 in a Syrian hamster SARS-CoV-2 infection model. Our findings suggest that cepharanthine is a potential therapeutic agent against COVID-19.

摘要

背景

由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的2019冠状病毒病(COVID-19)仍然是全球公共卫生威胁。尽管已经开发出几种有效的疫苗和治疗方法,但新变种的不断出现使得开发具有不同作用机制的药物成为必要。最近的研究表明,从千金藤中纯化得到的化学衍生物粉防己碱在体外可抑制SARS-CoV-2复制。

方法

本研究使用叙利亚仓鼠SARS-CoV-2感染模型研究了粉防己碱的体内作用。为评估预防和治疗效果,在SARS-CoV-2感染之前或之后经鼻给予粉防己碱。通过监测体重变化、肺部病理学、肺病毒载量和肺部炎症反应来评估效果。

结果

感染前给予粉防己碱导致体重减轻较少、病毒滴度降低、组织病理学严重程度减轻以及肺部炎症减轻。此外,感染后给予粉防己碱也表现出治疗效果。

结论

本研究表明,在叙利亚仓鼠SARS-CoV-2感染模型中,预防性和治疗性给予粉防己碱均可降低COVID-19的发病机制。我们的研究结果表明,粉防己碱是一种潜在的抗COVID-19治疗药物。

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