在 A549 细胞中临时表达融合了荧光蛋白 mRuby3 的 SARS-CoV-2 病毒 N 蛋白的模块化纳米转运体可引起该蛋白的胞内降解

IF 0.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Doklady Biochemistry and Biophysics Pub Date : 2024-02-20 DOI:10.1134/S1607672923700710
Y. V. Khramtsov, A. V. Ulasov, T. N. Lupanova,  G. P. Georgiev,  A. S. Sobolev
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引用次数: 0

摘要

我们创建了模块化纳米转运体(MNTs),其中含有一种类似于抗体的分子(单体),可与 SARS-CoV-2 病毒的 N 蛋白结合,还含有一种可诱导 Keap1 E3 连接酶(E3BP)的氨基酸序列。这种 MNT 还包括一个用于在酸性内细胞区室中将 E3BP 单体从 MNT 上裂解的位点。研究表明,内泌体蛋白酶 cathepsin B 的这种裂解会使 E3BP 单体对 N 蛋白的亲和力增加 2.7 倍。使用瞬时表达与荧光蛋白 mRuby3 融合的 N 蛋白的 A549 细胞,结果表明与 MNT 一起孵育会导致 mRuby3 荧光显著降低。据推测,所开发的 MNT 可作为开发针对 SARS-CoV-2 病毒的新型抗病毒药物的基础。
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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Modular Nanotransporters Capable of Causing Intracellular Degradation of the N-Protein of the SARS-CoV-2 Virus in A549 Cells with Temporary Expression of This Protein Fused with a Fluorescent Protein mRuby3

Modular nanotransporters (MNTs) containing an antibody-like molecule, monobody, to the N‑protein of the SARS-CoV-2 virus, as well as an amino acid sequence that recruits the Keap1 E3 ligase (E3BP) were created. This MNT also included a site for cleavage of the E3BP monobody from the MNT in acidic endocytic compartments. It was shown that this cleavage by the endosomal protease cathepsin B leads to a 2.7-fold increase in the affinity of the E3BP monobody for the N-protein. Using A549 cells with transient expression of the N-protein fused with the fluorescent protein mRuby3, it was shown that incubation with MNT leads to a significant decrease in mRuby3 fluorescence. It is assumed that the developed MNTs can serve as a basis for the creation of new antiviral drugs against the SARS-CoV-2 virus.

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来源期刊
Doklady Biochemistry and Biophysics
Doklady Biochemistry and Biophysics 生物-生化与分子生物学
CiteScore
1.60
自引率
12.50%
发文量
68
审稿时长
6-12 weeks
期刊介绍: Doklady Biochemistry and Biophysics is a journal consisting of English translations of articles published in Russian in biochemistry and biophysics sections of the Russian-language journal Doklady Akademii Nauk. The journal''s goal is to publish the most significant new research in biochemistry and biophysics carried out in Russia today or in collaboration with Russian authors. The journal accepts only articles in the Russian language that are submitted or recommended by acting Russian or foreign members of the Russian Academy of Sciences. The journal does not accept direct submissions in English.
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