沙特阿拉伯巴哈地区循环的奥密克戎SARS-CoV-2谱系的突变分析

Mutational Analysis of Circulating Omicron SARS-CoV-2 Lineages in the Al-Baha Region of Saudi Arabia.

作者信息

Almalki Shaia S R, Izhari Mohammad Asrar, Alyahyawi Hanan E, Alatawi Saleha Keder, Klufah Faisal, Ahmed Waled A M, Alharbi Raed

机构信息

Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Al-Baha University, Al-Baha, Saudi Arabia.

Department of Optometry, Faculty of Applied Medical Sciences, Al-Baha University, Al-Baha, Saudi Arabia.

出版信息

J Multidiscip Healthc. 2023 Jul 27;16:2117-2136. doi: 10.2147/JMDH.S419859. eCollection 2023.

DOI:10.2147/JMDH.S419859

PMID:37529147

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10389082/

Abstract

PURPOSE

Omicron (B.1.1.529) is one of the highly mutated variants of concern of SARS-CoV-2. Lineages of Omicron bear a remarkable degree of mutations leading to enhanced pathogenicity and upward transmission trajectory. Mutating Omicron lineages may trigger a fresh COVID-19 wave at any time in any region. We aimed at the whole-genome sequencing of SARS-CoV-2 to determine variants/subvariants and significant mutations which can foster virus evolution, monitoring of disease spread, and outbreak management.

METHODS

We used Illumina-NovaSeq 6000 for SARS-CoV-2 genome sequencing, MEGA 10.2 and nextstrain tools for phylogeny; CD-HIT program (version 4.8.1) and MUSCLE program for clustering and alignment. At the same time, UCSF Chimera was employed for protein visualization.

RESULTS

Predominant Omicron pango lineages in Al-Baha were BA.5.2/B22 (n=4, 57%), and other lineages were BA.2.12/21L (n=1, 14.28%), BV.1/22B (n=1, 14.28%) and BA.5.2.18/22B (n=1, 14.28%). 22B nextstrain clade was predominant, while only one lineage showed 21L. BA.5.2/22B, BA.5.2/22B harbored a maximum of n=24 mutations in the spike region. Twelve crucial RBD mutations: D405N, R408S, K417N, N440K, L452R, S477N, T478K, E484A, F486V, Q498R, N501Y, and Y505H were identified except the lineage BA.5.2/22B in which F486V mutation was not observed. Critical deletions S106 in membrane protein NSP6, E31in nucleocapsid, and L24 in spike region were observed in all the lineages. Furthermore, we identified common mutations of Omicron variants of SARS-CoV-2 in therapeutic hot spot spike region: T19I, D405N, R408S, K417N, N440K, L452R, S477N, T478K, E484A, F486V, Q498R, N501Y, Y505H, D614G, A653V, H655Y, N679K, P681H, N764K, D796Y, Q954H, N969K, D1146D, L452R, F486V, N679K and D796Y. The effect of RBD-targeted mutations on neutralizing (NAbs) binding was considerable.

CONCLUSION

The outcome of this first report on SARS-CoV-2 variants identification and mutation in the Al-Baha region could be used to lay down the policies to manage and impede the regional outbreak of COVID-19 effectively.

摘要

目的

奥密克戎（B.1.1.529）是严重急性呼吸综合征冠状病毒2（SARS-CoV-2）中高度变异的关注变体之一。奥密克戎谱系具有显著程度的突变，导致致病性增强和传播轨迹上升。变异的奥密克戎谱系可能在任何地区的任何时间引发新一波新冠疫情。我们旨在对SARS-CoV-2进行全基因组测序，以确定可促进病毒进化、监测疾病传播和疫情管理的变体/亚变体及重要突变。

方法

我们使用Illumina-NovaSeq 6000进行SARS-CoV-2基因组测序，使用MEGA 10.2和nextstrain工具进行系统发育分析；使用CD-HIT程序（版本4.8.1）和MUSCLE程序进行聚类和比对。同时，使用UCSF Chimera进行蛋白质可视化。

结果

巴哈省主要的奥密克戎谱系分类是BA.5.2/B22（n = 4，占57%），其他谱系为BA.2.12/21L（n = 1，占14.28%）、BV.1/22B（n = 1，占14.28%）和BA.5.2.18/22B（n = 1，占14.28%）。nextstrain进化枝22B占主导，而只有一个谱系显示为21L。BA.5.2/22B在刺突区域最多有n = 24个突变。除了未观察到F486V突变的BA.5.2/22B谱系外，还鉴定出12个关键的受体结合域（RBD）突变：D405N、R408S、K417N、N440K、L452R、S477N、T478K、E484A、F486V、Q498R、N501Y和Y505H。在所有谱系中均观察到膜蛋白NSP6中的关键缺失S106、核衣壳中的E31以及刺突区域中的L24。此外，我们在治疗热点刺突区域鉴定出SARS-CoV-2奥密克戎变体的常见突变：T19I、D405N、R408S、K417N、N440K、L452R、S477N、T478K、E484A、F486V、Q498R、N501Y、Y505H、D614G、A653V、H655Y、N679K、P681H、N764K、D796Y、Q954H、N969K、D1146D、L452R、F486V、N679K和D796Y。靶向RBD的突变对中和（NAbs）结合的影响相当大。