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比较 SARS-CoV-2 的基因组景观并鉴定与感染起源和多样性相关的突变。

Comparative insight into the genomic landscape of SARS-CoV-2 and identification of mutations associated with the origin of infection and diversity.

机构信息

Department of Plant Pathology, Kansas State University, Kansas, USA.

California Baptist University, Riverside, California, USA.

出版信息

J Med Virol. 2021 Apr;93(4):2406-2419. doi: 10.1002/jmv.26744. Epub 2020 Dec 29.

DOI:10.1002/jmv.26744
PMID:33347622
Abstract

The analyses of 2325 severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genomes revealed 107, 162, and 65 nucleotide substitutions in the coding region of SARS-CoV-2 from the three continents America, Europe, and Asia, respectively. Of these nucleotide substitutions 58, 94, and 37 were nonsynonymous types mostly present in the Nsp2, Nsp3, Spike, and ORF9. A continent-specific phylogram analyses clustered the SARS-CoV-2 in the different group based on the frequency of nucleotide substitutions. Detailed analyses about the continent-specific amino acid changes and their effectiveness by SNAP2 software was investigated. We found 11 common nonsynonymous mutations; among them, two novel effective mutations were identified in ORF9 (S194L and S202N). Intriguingly, ORF9 encodes nucleocapsid phosphoprotein possessing many effective mutations across continents and could be a potential candidate after the spike protein for studying the role of mutation in viral assembly and pathogenesis. Among the two forms of certain frequent mutation, one form is more prevalent in Europe continents (Nsp12:L314, Nsp13:P504, Nsp13:Y541, Spike:G614, and ORF8:L84) while other forms are more prevalent in American (Nsp12:P314, Nsp13:L504, Nsp13:C541, Spike:D614, and ORF8:L84) and Asian continents (Spike:D614), indicating the spatial and temporal dynamics of SARS-CoV-2. We identified highly conserved 38 regions and among these regions, 11 siRNAs were predicted on stringent criteria that can be used to suppress the expression of viral genes and the corresponding reduction of human viral infections. The present investigation provides information on different mutations and will pave the way for differentiating strains based on virulence and their use in the development of better antiviral therapy.

摘要

对来自美洲、欧洲和亚洲的 2325 株严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)基因组的分析显示,SARS-CoV-2 编码区分别有 107、162 和 65 个核苷酸取代。这些核苷酸取代中有 58、94 和 37 个是非同义类型,主要存在于 Nsp2、Nsp3、Spike 和 ORF9 中。基于核苷酸取代的频率,大陆特异性系统发育树分析将 SARS-CoV-2 聚类到不同的组中。详细分析了 SNAP2 软件的大陆特异性氨基酸变化及其有效性。我们发现了 11 个常见的非同义突变;其中,在 ORF9 中鉴定出两个新的有效突变(S194L 和 S202N)。有趣的是,ORF9 编码核衣壳磷蛋白,在各大洲都有许多有效的突变,它可能是继 Spike 蛋白之后研究突变在病毒组装和发病机制中的作用的一个潜在候选者。在某些频繁突变的两种形式中,一种形式在欧洲大陆更为普遍(Nsp12:L314、Nsp13:P504、Nsp13:Y541、Spike:G614 和 ORF8:L84),而另一种形式则更为普遍在美洲(Nsp12:P314、Nsp13:L504、Nsp13:C541、Spike:D614 和 ORF8:L84)和亚洲大陆(Spike:D614),表明 SARS-CoV-2 的空间和时间动态。我们鉴定了高度保守的 38 个区域,在这些区域中,根据严格的标准预测了 11 个 siRNA,可以用于抑制病毒基因的表达和相应减少人类病毒感染。本研究提供了不同突变的信息,为基于毒力区分菌株以及开发更好的抗病毒治疗方法铺平了道路。

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