Inhibitory effect of Alantolactone against varicella-zoster virus in vitro.

IF 4 3区医学 Q2 VIROLOGY

Virology Journal Pub Date : 2025-05-09 DOI:10.1186/s12985-025-02759-x

Xinna Wu, Yunchuang Chang, Chengcheng Kong, Zhiwei Ding, Dongli Pan, Ping Lin, Sanying Wang, Genxiang Mao

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引用次数: 0

Abstract

Background: Varicella-zoster virus (VZV), a member of the α-herpesvirus family, is known for causing two distinct diseases: chickenpox (varicella) during the primary infection and shingles (zoster) due to reactivation of the virus later in life. Although there are vaccines available to prevent VZV infection, it is still not universally effective, and antiviral treatments for VZV are limited and may come with significant side effects. Thus, development of novel therapeutics is urgently needed.

Methods: We identified a naturally occurring Alantolactone (ALT) that inhibited replication of recombinant VZV in human diploid fibroblast (WI-38 cells) and Adult Retinal Pigment Epithelial cell line-19 (ARPE-19 cells) through Western blotting, qPCR and plaque assays. Subsequently, we explored the mechanism underlying the anti-VZV activity of ALT using time-of-addition experiments and transcriptomic analyses.

Results: A screening model was established for anti-VZV compounds, and we screened ALT was with good anti-VZV efficacy. Our findings revealed that ALT alleviated cytopathic changes, reduced viral titres, and inhibited the expression of viral genes and proteins in WI-38 cells and ARPE-19 cells. Furthermore, our data showed that ALT inhibited VZV infection in intracellular viral replication. Finally, multiple inflammatory pathways were involved in the antiviral role of ALT, and IL-6 was one of the most critical hub genes.

Conclusion: Together, our findings identify ALT as an anti-VZV agent that may prove useful in the treatment of VZV replication.

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阿兰妥内酯对水痘-带状疱疹病毒体外抑制作用的研究。

背景：水痘-带状疱疹病毒（VZV）是α-疱疹病毒家族的一员，以引起两种不同的疾病而闻名：水痘（水痘）在初次感染期间和带状疱疹（带状疱疹）由于病毒在生命后期的再激活。虽然有疫苗可以预防VZV感染，但它仍然不是普遍有效的，VZV的抗病毒治疗是有限的，可能会有明显的副作用。因此，迫切需要开发新的治疗方法。方法：通过Western blotting、qPCR和斑块分析，我们鉴定了一种天然存在的Alantolactone （ALT）能够抑制重组VZV在人二倍体成纤维细胞（WI-38细胞）和成人视网膜色素上皮细胞系19 （ARPE-19细胞）中的复制。随后，我们通过添加时间实验和转录组学分析探讨了ALT抗vzv活性的机制。结果：建立了抗vzv化合物筛选模型，筛选出的ALT具有较好的抗vzv效果。结果表明，ALT可减轻WI-38细胞和ARPE-19细胞的病变，降低病毒滴度，抑制病毒基因和蛋白的表达。此外，我们的数据表明，ALT抑制VZV感染的细胞内病毒复制。最后，多种炎症途径参与了ALT的抗病毒作用，IL-6是其中最关键的枢纽基因之一。结论：总之，我们的研究结果确定ALT是一种抗VZV药物，可能被证明对VZV复制的治疗有用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Virology Journal 医学-病毒学

CiteScore

7.40

自引率

2.10%

发文量

186

审稿时长

1 months

期刊介绍： Virology Journal is an open access, peer reviewed journal that considers articles on all aspects of virology, including research on the viruses of animals, plants and microbes. The journal welcomes basic research as well as pre-clinical and clinical studies of novel diagnostic tools, vaccines and anti-viral therapies. The Editorial policy of Virology Journal is to publish all research which is assessed by peer reviewers to be a coherent and sound addition to the scientific literature, and puts less emphasis on interest levels or perceived impact.