In vitro enzyme characterization and several inhibitors for monkeypox virus core protease I7L.

IF 2.2 4区生物学 Q3 MICROBIOLOGY

Fems Microbiology Letters Pub Date : 2025-01-17 DOI:10.1093/femsle/fnaf008

Lin Wei, Yuqi Wu, Shuai Li, Jun Weng, Miaomiao Geng, Meng Mei, Zigong Wei

引用次数: 0

Abstract

Monkeypox is a zoonotic viral disease caused by the monkeypox virus, a member of the genus Orthopoxvirus within the family Poxviridae, which also includes the variola virus. On Aug. 14, 2024, WHO Director-General declared monkeypox outbreak a public health emergency of international concern. Similar to variola virus core protease K7L, the I7L could be identified as a promising target to against monkeypox virus. Our work provides a solid foundation as well as specific molecular tools (protease production methods, assay design, inhibitor design) that can now be used to probe the function of I7L in vitro. Notably, in this work, various reported covalent lead compounds for COVID-19 proteases were screened and A68, shikonin and myricetin were identified as exhibiting high inhibitory activity against I7L. This work not only sheds light on effective inhibitors for the monkeypox virus core protease but also contributes to the broader search for antiviral agents targeting this enzyme.

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猴痘病毒核心蛋白酶I7L的体外酶学特性及几种抑制剂。

猴痘是由猴痘病毒引起的一种人畜共患病毒性疾病，猴痘病毒是痘病毒科正痘病毒属的一员，也包括天花病毒。2024年8月14日，世卫组织总干事宣布猴痘疫情为国际关注的突发公共卫生事件。与天花病毒核心蛋白酶K7L相似，I7L可作为抗猴痘病毒的一个有希望的靶点。我们的工作提供了一个坚实的基础，以及特定的分子工具（蛋白酶生产方法，实验设计，抑制剂设计），现在可以用来探测I7L的体外功能。值得注意的是，本研究筛选了多种已报道的COVID-19蛋白酶共价先导化合物，并鉴定出A68、紫草素和杨梅素对I7L具有较高的抑制活性。这项工作不仅揭示了猴痘病毒核心蛋白酶的有效抑制剂，而且有助于更广泛地寻找针对该酶的抗病毒药物。

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

Fems Microbiology Letters 生物-微生物学

CiteScore

4.30

自引率

0.00%

发文量

112

审稿时长

1.9 months

期刊介绍： FEMS Microbiology Letters gives priority to concise papers that merit rapid publication by virtue of their originality, general interest and contribution to new developments in microbiology. All aspects of microbiology, including virology, are covered. 2019 Impact Factor: 1.987, Journal Citation Reports (Source Clarivate, 2020) Ranking: 98/135 (Microbiology) The journal is divided into eight Sections: Physiology and Biochemistry (including genetics, molecular biology and ‘omic’ studies) Food Microbiology (from food production and biotechnology to spoilage and food borne pathogens) Biotechnology and Synthetic Biology Pathogens and Pathogenicity (including medical, veterinary, plant and insect pathogens – particularly those relating to food security – with the exception of viruses) Environmental Microbiology (including ecophysiology, ecogenomics and meta-omic studies) Virology (viruses infecting any organism, including Bacteria and Archaea) Taxonomy and Systematics (for publication of novel taxa, taxonomic reclassifications and reviews of a taxonomic nature) Professional Development (including education, training, CPD, research assessment frameworks, research and publication metrics, best-practice, careers and history of microbiology) If you are unsure which Section is most appropriate for your manuscript, for example in the case of transdisciplinary studies, we recommend that you contact the Editor-In-Chief by email prior to submission. Our scope includes any type of microorganism - all members of the Bacteria and the Archaea and microbial members of the Eukarya (yeasts, filamentous fungi, microbial algae, protozoa, oomycetes, myxomycetes, etc.) as well as all viruses.