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计算机模拟研究 SARS-CoV-2 蛋白的突变稳定性。

In Silico Study of Mutational Stability of SARS-CoV-2 Proteins.

机构信息

Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata, 700073, India.

出版信息

Protein J. 2021 Jun;40(3):328-340. doi: 10.1007/s10930-021-09988-3. Epub 2021 Apr 22.

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), an enveloped RNA virus transmits by droplet infection thus affects the respiratory system. Different genomes have been reported globally for SARS-CoV-2 with moderate level of mutation which makes it harder to combat the virus. Mutational profiling and the relevant evolutionary aspect of coronavirus proteins namely spike glycoprotein, membrane protein, envelope protein, nucleoprotein, ORF1ab, ORF3a, ORF6, ORF7a, ORF7b and ORF8 were studied by in silico experiments. Clustering of the protein sequences and calculation of residue relative abundance were done to get an idea about the protein conservancy as well as finding out some representative sequences for phylogenetic and ancestral reconstruction. By mutational profiling and mutation analysis, the effect of mutations on the protein stability and their functional implication were studied. This study indicates the mutational effect on the proteins and their relevance in evolution, which directs us towards a better understanding of these variations and diversification of SARS-CoV-2 for useful future therapeutic study and thus aid in designing therapeutic agents keeping the highly variable regions in mind.

摘要

严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)是一种包膜 RNA 病毒,通过飞沫感染传播,从而影响呼吸系统。目前全球已报告了多种 SARS-CoV-2 基因组,其突变程度中等,这使得对抗病毒变得更加困难。通过计算机实验研究了冠状病毒蛋白的突变分析和相关进化方面,即刺突糖蛋白、膜蛋白、包膜蛋白、核衣壳蛋白、ORF1ab、ORF3a、ORF6、ORF7a、ORF7b 和 ORF8。对蛋白质序列进行聚类和残基相对丰度的计算,以了解蛋白质的保守性,并找到一些具有代表性的序列进行系统发育和祖先重建。通过突变分析和突变分析,研究了突变对蛋白质稳定性的影响及其功能意义。本研究表明了突变对蛋白质的影响及其在进化中的相关性,这使我们能够更好地理解这些 SARS-CoV-2 的变异和多样化,为未来的治疗研究提供有用的指导,从而有助于设计治疗剂,牢记高度可变区域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ee/8061876/1a53a9cf7d13/10930_2021_9988_Fig1_HTML.jpg

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