抗霉素A通过破坏嘧啶体的形成来抑制-疱疹病毒的复制

IF 11.4 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Journal of Advanced Research Pub Date : 2025-05-10 DOI:10.1016/j.jare.2025.05.016

Yong-Qi Guo, Meng-Hang Wang, Ning Tang, Yu-Bo Zhao, Li-Jing Wo, De-Xin Liang, Rui Huang, Yan-Dong Tang, Ying-Jie Sun, Xin Yin

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引用次数: 0

摘要

甲型疱疹病毒对人类健康构成重大风险，并对畜牧业构成挑战。目前，临床批准的抗病毒药物阿昔洛韦显示出局限性，包括耐药和不良反应。目前迫切需要研制广谱抗病毒药物。目的寻找一种广泛抑制多种α -疱疹病毒的新型抗病毒药物。方法在本研究中，我们对1500种化合物进行了高含量筛选，以确定潜在的抗病毒候选化合物。通过表型实验、非靶向代谢组学和分子对接等方法探索抗病毒机制。结果我们发现抗霉素A能有效抑制多种α -疱疹病毒的复制，包括单纯疱疹病毒1 （HSV-1）、牛疱疹病毒1 （BHV-1）和伪狂犬病毒（PRV）。我们的研究表明，抗霉素A通过破坏嘧啶体的形成来抑制病毒复制，嘧啶体是有效病毒感染所必需的。最后，在prv感染的BALB/c小鼠中，antiycin A能有效抑制病毒感染，防止组织损伤，提高小鼠存活率，证实了其在体内的有效性。结论抗霉素A是开发抗α -疱疹病毒感染抗病毒药物的重要候选药物。

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Antimycin A inhibits alpha-herpesvirus replication by disrupting the formation of pyrimidinosomes

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Antimycin A inhibits alpha-herpesvirus replication by disrupting the formation of pyrimidinosomes

Introduction

Alpha-herpesvirus poses significant health risks to humans and challenges to animal husbandry. Currently, the clinically approved antiviral drug Acyclovir exhibits limitations, including drug resistance and adverse effects. The development of broad-spectrum antiviral agents against alpha-herpesvirus is urgently needed.

Objective

This study aimed to discover a novel antiviral drug with the capacity to broadly inhibit various alpha-herpesviruses.

Methods

In this study, we conducted a high-content screening of 1,500 chemical compounds to identify potential antiviral candidates. The antiviral mechanisms were explored using phenotypic experiments, untargeted metabolomics, and molecular docking.

Results

We discovered that Antimycin A effectively inhibits the replication of various alpha-herpesviruses, including herpes simplex virus 1 (HSV-1), bovine herpesvirus 1 (BHV-1), and pseudorabies virus (PRV). Our study revealed that Antimycin A inhibits viral replication by disrupting the formation of pyrimidinosomes that are essential for efficient viral infection. Finally, Antimycin A effectively inhibited viral infection, prevented tissue damage, and enhanced survival in PRV-infected BALB/c mice, confirming its in vivo efficacy.

Conclusion

Antimycin A emerges as a promising lead candidate for the development of antiviral therapies against alpha-herpesvirus infections.

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来源期刊

Journal of Advanced Research Multidisciplinary-Multidisciplinary

CiteScore

21.60

自引率

0.90%

发文量

280

审稿时长

12 weeks

期刊介绍： Journal of Advanced Research (J. Adv. Res.) is an applied/natural sciences, peer-reviewed journal that focuses on interdisciplinary research. The journal aims to contribute to applied research and knowledge worldwide through the publication of original and high-quality research articles in the fields of Medicine, Pharmaceutical Sciences, Dentistry, Physical Therapy, Veterinary Medicine, and Basic and Biological Sciences. The following abstracting and indexing services cover the Journal of Advanced Research: PubMed/Medline, Essential Science Indicators, Web of Science, Scopus, PubMed Central, PubMed, Science Citation Index Expanded, Directory of Open Access Journals (DOAJ), and INSPEC.