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利用计算机模拟方法鉴定土耳其分离的 SARS-CoV-2 核衣壳蛋白突变的结构和功能特征。

Structural and functional characterization of SARS-CoV-2 nucleocapsid protein mutations identified in Turkey by using in silico approaches.

出版信息

Acta Virol. 2023;67(1):59-68. doi: 10.4149/av_2023_106.

Abstract

Missense mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus may cause changes in the structure of proteins. The nucleocapsid (N) protein is an important target for drugs and vaccines. The main purpose of this study is to detect missense mutations in the SARS-CoV-2 N protein and to reveal the effects of these mutations on protein structure by using in silico approaches. 161 missense mutations of the N protein were determined in 2286 SARS-CoV-2 genomes derived from the GISAID EpiCoV database in the Turkish population. Identified 161 missense mutations were analyzed by using sequence and structure-based methods to predict effects of mutation on function and structure of SARS-CoV-2 N protein. These analyzes revealed that some mutations showed deleterious effects and change of stability and flexibility of nucleocapsid protein. D3L, S194L, S235F, and P13L (Omicron variant) mutations were further analyzed in our study due to their importance in the literature and in our results. Even though, our findings are essential for research of SARS-CoV-2 virus, in vitro and in vivo validations are necessary. Keywords: nucleocapsid protein; SARS-CoV-2; missense mutations; protein stability; protein flexibility.

摘要

严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 病毒中的错义突变可能导致蛋白质结构发生变化。核衣壳 (N) 蛋白是药物和疫苗的重要靶点。本研究的主要目的是通过计算方法检测 SARS-CoV-2 N 蛋白中的错义突变,并揭示这些突变对蛋白质结构的影响。从 GISAID EpiCoV 数据库中提取了土耳其人群的 2286 个 SARS-CoV-2 基因组,确定了 N 蛋白中的 161 个错义突变。通过使用序列和基于结构的方法分析鉴定出的 161 个错义突变,以预测突变对 SARS-CoV-2 N 蛋白功能和结构的影响。这些分析表明,一些突变具有有害影响,并改变了核衣壳蛋白的稳定性和柔韧性。由于这些突变在文献和我们的结果中具有重要性,因此我们进一步分析了 D3L、S194L、S235F 和 P13L(Omicron 变体)突变。尽管我们的发现对 SARS-CoV-2 病毒的研究很重要,但仍需要进行体外和体内验证。关键词:核衣壳蛋白;严重急性呼吸综合征冠状病毒 2;错义突变;蛋白质稳定性;蛋白质柔韧性。

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