Baicalein suppresses Coxsackievirus B3 replication by inhibiting caspase-1 and viral protease 2A

Yanyan Dong; Enze Shao; Siwei Li; Ruiqi Wang; Dan Wang; Lixin Wang; Hong Yang; Yingxia He; Tian Luan; Yang Chen; Yao Wang; Lexun Lin; Yan Wang; Zhaohua Zhong; Wenran Zhao

doi:10.1016/j.virs.2024.07.003

August 2024

Yanyan Dong, Enze Shao, Siwei Li, Ruiqi Wang, Dan Wang, Lixin Wang, Hong Yang, Yingxia He, Tian Luan, Yang Chen, Yao Wang, Lexun Lin, Yan Wang, Zhaohua Zhong and Wenran Zhao. Baicalein suppresses Coxsackievirus B3 replication by inhibiting caspase-1 and viral protease 2A[J]. Virologica Sinica, 2024, 39(4): 685-693. doi: 10.1016/j.virs.2024.07.003

Citation: Yanyan Dong, Enze Shao, Siwei Li, Ruiqi Wang, Dan Wang, Lixin Wang, Hong Yang, Yingxia He, Tian Luan, Yang Chen, Yao Wang, Lexun Lin, Yan Wang, Zhaohua Zhong, Wenran Zhao. Baicalein suppresses Coxsackievirus B3 replication by inhibiting caspase-1 and viral protease 2A .VIROLOGICA SINICA, 2024, 39(4) : 685-693. http://dx.doi.org/10.1016/j.virs.2024.07.003

黄芩素通过抑制Caspase-1及病毒2A蛋白酶发挥抗B组3型柯萨奇病毒作用

董艳艳 ^a ,
邵恩泽 ^a ,
李思葳 ^a ,
王瑞琦 ^a ,
王丹 ^a ,
王立鑫 ^a ,
杨虹 ^a ,
何颖霞 ^a ,
栾天 ^a ,
陈阳 ^b ,
王瑶 ^a ,
林乐勋 ^a ,
王燕 ^b ,
钟照华 ^b,, ,
赵文然 ^a,,

cstr: 32224.14.j.virs.2024.07.003

a. Department of Cell Biology, Harbin Medical University, Harbin 150081, China;
b. Department of Microbiology, Harbin Medical University, Harbin 150081, China

通讯作者： 钟照华, zhongzh@hrbmu.edu.cn; 赵文然, zhaowr@hrbmu.edu.cn
收稿日期： 2024-01-09
录用日期： 2024-07-12

摘要

心肌炎是心肌组织的炎症性疾病，常见于儿童和青年，是扩张型心肌病的主要病因。B组柯萨奇病毒（Coxsackievirus B, CVB）是导致病毒性心肌炎的重要病原体。由于缺乏疫苗，抗病毒药物则成为控制CVB感染和心肌炎进展的重要手段。黄芩素为提取自黄芩（Scutellaria baicaleinsis）的黄酮类化合物，具有抗炎、抗氧化、抗肿瘤等多种生物学活性。本研究观察了黄芩素（baicalein）的抗CVB作用。结果表明，用黄芩素处理CVB3感染细胞，细胞病变受到显著抑制，细胞活力显著升高；此外，病毒3D蛋白、病毒RNA和病毒粒子的产生均显著下降。动物实验表明，黄芩素处理后，小鼠心肌组织炎症反应明显减轻，病毒在心肌组织中的复制受到明显抑制，小鼠存活率显著提高。进一步研究发现，黄芩素的抗病毒作用与其对caspase-1和病毒2A蛋白酶的抑制有关。本研究结果表明，黄芩素能有效抑制CVB3复制及病毒性心肌炎，因此，可能成为潜在的抗CVB药物。
- 黄芩素
- , B组3型柯萨奇病毒
- , 心肌炎
- , 2A蛋白酶
- , Caspase-1

Baicalein suppresses Coxsackievirus B3 replication by inhibiting caspase-1 and viral protease 2A

Yanyan Dong ^a ,
Enze Shao ^a ,
Siwei Li ^a ,
Ruiqi Wang ^a ,
Dan Wang ^a ,
Lixin Wang ^a ,
Hong Yang ^a ,
Yingxia He ^a ,
Tian Luan ^a ,
Yang Chen ^b ,
Yao Wang ^a ,
Lexun Lin ^a ,
Yan Wang ^b ,
Zhaohua Zhong ^b,, ,
Wenran Zhao ^a,,

a. Department of Cell Biology, Harbin Medical University, Harbin 150081, China;
b. Department of Microbiology, Harbin Medical University, Harbin 150081, China

Corresponding author: Zhaohua Zhong, zhongzh@hrbmu.edu.cn Wenran Zhao, zhaowr@hrbmu.edu.cn
Received Date: 09 January 2024
Accepted Date: 12 July 2024

Abstract

Myocarditis is an inflammatory disease of the cardiac muscle and one of the primary causes of dilated cardiomyopathy. Group B coxsackievirus (CVB) is one of the leading causative pathogens of viral myocarditis, which primarily affects children and young adults. Due to the lack of vaccines, the development of antiviral medicines is crucial to controlling CVB infection and the progression of myocarditis. In this study, we investigated the antiviral effect of baicalein, a flavonoid extracted from Scutellaria baicaleinsis. Our results demonstrated that baicalein treatment significantly reduced cytopathic effect and increased cell viability in CVB3-infected cells. In addition, significant reductions in viral protein 3D, viral RNA, and viral particles were observed in CVB3-infected cells treated with baicalein. We found that baicalein exerted its inhibitory effect in the early stages of CVB3 infection. Baicalein also suppressed viral replication in the myocardium and effectively alleviated myocarditis induced by CVB3 infection. Our study revealed that baicalein exerts its antiviral effect by inhibiting the activity of caspase-1 and viral protease 2A. Taken together, our findings demonstrate that baicalein has antiviral activity against CVB3 infection and may serve as a potential therapeutic option for the myocarditis caused by enterovirus infection.
- Baicalein
- , Coxsackievirus B (CVB)
- , Myocarditis
- , 2A protease
- , Caspase-1

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10.1016j.virs.2024.07.003-ESM.docx