青蒿甙 B4 可抑制 SARS-CoV-2 在体外和体内的复制

IF 4.7 4区 医学 Q1 CHEMISTRY, MEDICINAL Chinese Herbal Medicines Pub Date : 2024-01-01 DOI:10.1016/j.chmed.2023.09.005
Mingyue Xiao , Ronghua Luo , Qinghua Liang , Honglv Jiang , Yanli Liu , Guoqiang Xu , Hongwei Gao , Yongtang Zheng , Qiongming Xu , Shilin Yang
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引用次数: 0

摘要

目的从白头翁中分离出的最丰富的三萜皂苷 B4(AB4)可抑制流感病毒 FM1 或肺炎克雷伯氏菌诱发的肺炎。然而,AB4 的抗 SARS-CoV-2 作用尚未被揭示。因此,本研究旨在确定 AB4 在体内和体外抑制人类冠状病毒 SARS-CoV-2 的抗病毒活性和潜在机制。体外试验使用了感染 SARS-CoV-2 的 HEK293T、HPAEpiC 和 Vero E6 细胞。通过SARS-CoV-2感染hACE2-IRES-luc转基因小鼠模型评估了AB4在体内的抗病毒作用。此外,还进行了无标记定量蛋白质组学和生物信息学分析,以探索 AB4 潜在的抗病毒作用机制。结果表明,AB4能降低SARS-CoV-2在HEK293T细胞中的传播,同时减少核头壳蛋白(N)、尖峰蛋白(S)和3C样蛋白酶(3CLpro)。体内抗病毒活性数据显示,AB4 可抑制病毒复制,并缓解 SARS-CoV-2 感染小鼠模型的肺炎。我们进一步发现,AB4 的抗病毒活性与通过激活类视黄酸诱导基因 I(RIG-1)受体(RLP)途径增强干扰素(IFN)-β 反应有关。此外,无标记定量蛋白质组分析发现,AB4 在 SARS-CoV-2 冠状病毒感染细胞中显著改变了 17 种蛋白质。结论我们的研究结果表明,AB4 通过 RLR 途径抑制了 SARS-CoV-2 的复制,并缓和了 RNA 代谢,这表明它将成为开发抗 SARS-CoV-2 药物的潜在先导化合物。
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Anemoside B4 inhibits SARS-CoV-2 replication in vitro and in vivo

Objective

Anemoside B4 (AB4), the most abundant triterpenoidal saponin isolated from Pulsatilla chinensis, inhibited influenza virus FM1 or Klebsiella pneumoniae-induced pneumonia. However, the anti-SARS-CoV-2 effect of AB4 has not been unraveled. Therefore, this study aimed to determine the antiviral activity and potential mechanism of AB4 in inhibiting human coronavirus SARS-CoV-2 in vivo and in vitro.

Methods

The cytotoxicity of AB4 was evaluated using the Cell Counting Kit-8 (CCK8) assay. SARS-CoV-2 infected HEK293T, HPAEpiC, and Vero E6 cells were used for in vitro assays. The antiviral effect of AB4 in vivo was evaluated by SARS-CoV-2-infected hACE2-IRES-luc transgenic mouse model. Furthermore, label-free quantitative proteomics and bioinformatic analysis were performed to explore the potential antiviral mechanism of action of AB4. Type I IFN signaling-associated proteins were assessed using Western blotting or immumohistochemical staining.

Results

The data showed that AB4 reduced the propagation of SARS-CoV-2 along with the decreased Nucleocapsid protein (N), Spike protein (S), and 3C-like protease (3CLpro) in HEK293T cells. In vivo antiviral activity data revealed that AB4 inhibited viral replication and relieved pneumonia in a SARS-CoV-2 infected mouse model. We further disclosed that the antiviral activity of AB4 was associated with the enhanced interferon (IFN)-β response via the activation of retinoic acid-inducible gene I (RIG-1) like receptor (RLP) pathways. Additionally, label-free quantitative proteomic analyses discovered that 17 proteins were significantly altered by AB4 in the SARS-CoV-2 coronavirus infections cells. These proteins mainly clustered in RNA metabolism.

Conclusion

Our results indicated that AB4 inhibited SARS-CoV-2 replication through the RLR pathways and moderated the RNA metabolism, suggesting that it would be a potential lead compound for the development of anti-SARS-CoV-2 drugs.

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来源期刊
Chinese Herbal Medicines
Chinese Herbal Medicines CHEMISTRY, MEDICINAL-
CiteScore
4.40
自引率
5.30%
发文量
629
审稿时长
10 weeks
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