Anemoside B4 inhibits SARS-CoV-2 replication in vitro and in vivo

Mingyue Xiao ¹Ronghua Luo ²Qinghua Liang ¹Honglv Jiang ³Yanli Liu ¹Guoqiang Xu ³Hongwei Gao ⁴Yongtang Zheng ²Qiongming Xu ¹Shilin Yang¹

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作者信息

1. College of Pharmaceutical Sciences,Soochow University,Suzhou 215123,China
2. Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences,KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming 650223,China
3. College of Pharmaceutical Sciences,Soochow University,Suzhou 215123,China;Jiangsu Key Laboratory of Neuropsychiatric Diseases and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases,Soochow University,Suzhou 215123,China
4. College of Pharmacy,Guangxi University of Chinese Medicine,Nanning 530000,China
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Abstract

Objective:Anemoside B4(AB4),the most abundant triterpenoidal saponin isolated from Pulsatilla chinen-sis,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 activ-ity 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 antivi-ral 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 pro-teins 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.

Key words

anemoside B4/interferon/RNA metabolism/quantitative proteomics/SARS-CoV-2

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基金项目

National Natural Science Foundation of China(82341087)

National Natural Science Foundation of China(82073912)

Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions()

出版年

2024

中草药(英文版)

天津药物研究院中国医学科学院药用植物研究所

中草药(英文版)

CSTPCD

影响因子：0.6

ISSN：1674-6384

参考文献量15

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