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酶法分析探索病毒 mRNA 加帽机制。

Enzymatic Assays to Explore Viral mRNA Capping Machinery.

机构信息

Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097, Warsaw, Poland.

College of Inter-Faculty Individual Studies in, Mathematics and Natural Sciences, University of Warsaw, Banacha 2c, 02-097, Warsaw, Poland.

出版信息

Chembiochem. 2021 Dec 2;22(23):3236-3253. doi: 10.1002/cbic.202100291. Epub 2021 Aug 3.

Abstract

In eukaryotes, mRNA is modified by the addition of the 7-methylguanosine (m G) 5' cap to protect mRNA from premature degradation, thereby enhancing translation and enabling differentiation between self (endogenous) and non-self RNAs (e. g., viral ones). Viruses often develop their own mRNA capping pathways to augment the expression of their proteins and escape host innate immune response. Insights into this capping system may provide new ideas for therapeutic interventions and facilitate drug discovery, e. g., against viruses that cause pandemic outbreaks, such as beta-coronaviruses SARS-CoV (2002), MARS-CoV (2012), and the most recent SARS-CoV-2. Thus, proper methods for the screening of large compound libraries are required to identify lead structures that could serve as a basis for rational antiviral drug design. This review summarizes the methods that allow the monitoring of the activity and inhibition of enzymes involved in mRNA capping.

摘要

在真核生物中,mRNA 通过添加 7-甲基鸟苷(mG)5'帽来修饰,以保护 mRNA 免受过早降解,从而增强翻译并区分自身(内源性)和非自身 RNA(例如,病毒 RNA)。病毒通常会开发自己的 mRNA 加帽途径来增加其蛋白质的表达并逃避宿主先天免疫反应。对该加帽系统的深入了解可能为治疗干预提供新的思路,并有助于药物发现,例如针对引起大流行爆发的病毒,如β冠状病毒 SARS-CoV(2002 年)、MARS-CoV(2012 年)和最近的 SARS-CoV-2。因此,需要适当的方法来筛选大型化合物文库,以鉴定可能作为合理抗病毒药物设计基础的先导结构。本文综述了监测参与 mRNA 加帽的酶的活性和抑制的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3a2/8426721/a69402d645f2/CBIC-22-3236-g006.jpg

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