江苏省新型冠状病毒NSP1变异分析及其与临床分型的关系

Variations in NSP1 of SARA-CoV-2 and the relationship with clinical typing in Jiangsu province

目的探讨江苏省新型冠状病毒(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)非结构蛋白1(nonstructural protein 1,NSPl)变异情况及其与临床分型的关系。方法收集2020—2022年间江苏省SARS-CoV-2感染病例的样本及基本临床信息。对样本进行高通量测序,测序后的数据以Wuhan-Hu-1(GenBank:MN908947.3)为参考基因分析NSP1序列变异情况及其与临床分型的关系。使用DynaMut在线服务器分析突变氨基酸对蛋白质稳定性及分子柔韧性的影响。结果共收集病例样本1241例,NSP1基因同义突变61例,错义突变及缺失共487例,存在氨基酸变异的患者以无症状感染者(75.4%)为主,且病例临床分型严重程度更轻(Z=-24.8,P<0.01)。共发现NSP1蛋白出现11个非同义突变和1个缺失。N端中出现了8个稳定突变及1个失稳突变,2个突变增加了分子柔韧性;Linker区S135R的突变使蛋白质失稳但增加了柔韧性;C端R171C突变使蛋白质稳定但降低了柔韧性。NSP1蛋白稳定性降低的患者临床分型症状更轻。结论NSP1部分氨基酸的改变使蛋白结构发生变化,可能降低病毒的致病力,导致较轻的临床症状。

Objective To explore the variations in non-structural protein 1(NSPl)of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and the relationship with clinical typing Jiangsu province.Methods Samples and basic clinical information of SARS-Cov-2 infected cases in Jiangsu province from 2020 to 2022 were collected.High-throughput sequencing was used to sequence these samples,and the genomic sequences were compared using Wuhan-Hu-1(GenBank:MN908947.3)as the reference sequence to analyze the variations in NSPl and the relationship with clinical typing.Using the DynaMut on-line tool to analyze the effects of amino acid mutations on the protein stability and molecular flexibility.Results A total of 1241 cases were collected.There were 61 synonymous mutations,487 non-synonymous mutation and deletions in NSP1 gene.The majority of cases with amino acid variations were asymptomatic infections(75.4%),and the clinical classification of cases severity was lower(Z=-24.8,P<0.01).A total of 11 non-synonymous mutations and 1 deletion in NSP1 were detected.Eight mutations exhibited a stabilizing effect in the N-terminal domain,two mutations increased molecular flexibility,while other mutations all decreased the flexibility.The mutation of S135R in the linker region caused protein destabilizing and increased its flexibility.The R171C mutation at the C-terminal domain exhibited a stabilizing effect but reduced the flexibility.Cases with destabilizing in NSP1 protein had lower severity in clinical classification.Conclusions Some changes of amino acids in NSP1 resulted in modification of protein structure,which may mitigate the virulence of the virus and result the relatively mild clinical symptoms.