Biological Significance of the Genomic Variation and Structural Dynamics of SARS-CoV-2 B.1.617.
Biological Significance of the Genomic Variation and Structural Dynamics of SARS-CoV-2 B.1.617.
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DOI：
10.3389/fmicb.2021.750725
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发表时间：
2021
影响因子：
5.2
通讯作者：
He JS
中科院分区：
文献类型：
--
作者：
Fan LQ;Hu XY;Chen YY;Peng XL;Fu YH;Zheng YP;Yu JM;He JS
自2019冠状病毒病疫情爆发以来，严重急性呼吸系统综合征冠状病毒2型（SARS-CoV-2）变异株不断出现并在全球传播，其中B. 1. 617谱系于2020年底首次在印度报告，并很快成为主要毒株。追踪基因组变异并了解其对病毒特性的影响是疫苗和药物开发以及采取或解除缓解措施的基础。在这项研究中，分析了属于B.1.617的1，051个接近完整的基因组和1，559个刺突（S）序列。单核苷酸多态性（SNP）的全基因组范围内的传播被确定。在鉴定的高频突变中，61%（11/18）涉及结构蛋白，尽管三分之二的病毒基因组编码非结构蛋白。结果表明，在S蛋白上有22个阳性选择位点，其中16个位点是由非C → U转换引起的，应引起特别注意。单倍型网络分析表明，在整个大流行期间，B.1.617.2的祖先单倍型H176不断衍生出大量的子代单倍型，其中H177、H181、H219和H286广泛流行。除了已知的L452 R、P681 R的取代和E156、F157的缺失以及潜在的生物学意义外，本研究的结构分析还表明，B.1.617中新的氨基酸变化，如E484 Q和N501 Y，重塑了病毒结合网络，在后续监测中，在许多其他国家检测到了具有潜在增强结合能力的N501 Y突变体。虽然我们不能完全确定包括N501 Y在内的所有突变体的特性，但值得关注的是它们在植物学和生物学上的传播。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have been emerging and circulating globally since the start of the COVID-19 pandemic, of which B.1.617 lineage that was first reported in India at the end of 2020, soon became predominant. Tracing genomic variations and understanding their impact on the viral properties are the foundations for the vaccine and drug development and for the mitigation measures to be taken or lifted. In this study, 1,051 near-complete genomes and 1,559 spike (S) sequences belonging to the B.1.617 were analyzed. A genome-wide spread of single nucleotide polymorphisms (SNPs) was identified. Of the high frequency mutations identified, 61% (11/18) involved structural proteins, despite two third of the viral genome encoding nonstructural proteins. There were 22 positive selection sites, mostly distributed across the S protein, of which 16 were led by non-C to U transition and should be of a special attention. Haplotype network revealed that a large number of daughter haplotypes were continually derived throughout the pandemic, of which H177, H181 H219 and H286 from the ancestor haplotype H176 of B.1.617.2 were widely prevalent. Besides the well known substitutions of L452R, P681R and deletions of E156 and F157, as well as the potential biological significance, structural analysis in this study still indicated that new amino acid changes in B.1.617, such as E484Q and N501Y, had reshaped the viral bonding network, and increasingly sequenced N501Y mutant with a potential enhanced binding ability was detected in many other countries in the follow-up monitoring. Although we can’t conclude the properties of all the mutants including N501Y thoroughly, it merits focusing on their spread epidemically and biologically.
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影响因子：
64.5
作者：
Liu C;Ginn HM;Dejnirattisai W;Supasa P;Wang B;Tuekprakhon A;Nutalai R;Zhou D;Mentzer AJ;Zhao Y;Duyvesteyn HME;López-Camacho C;Slon-Campos J;Walter TS;Skelly D;Johnson SA;Ritter TG;Mason C;Costa Clemens SA;Gomes Naveca F;Nascimento V;Nascimento F;Fernandes da Costa C;Resende PC;Pauvolid-Correa A;Siqueira MM;Dold C;Temperton N;Dong T;Pollard AJ;Knight JC;Crook D;Lambe T;Clutterbuck E;Bibi S;Flaxman A;Bittaye M;Belij-Rammerstorfer S;Gilbert SC;Malik T;Carroll MW;Klenerman P;Barnes E;Dunachie SJ;Baillie V;Serafin N;Ditse Z;Da Silva K;Paterson NG;Williams MA;Hall DR;Madhi S;Nunes MC;Goulder P;Fry EE;Mongkolsapaya J;Ren J;Stuart DI;Screaton GR
通讯作者：
Screaton GR
影响因子：
2.7
作者：
Berrio A;Gartner V;Wray GA
通讯作者：
Wray GA
影响因子：
5
作者：
Emam M;Oweda M;Antunes A;El-Hadidi M
通讯作者：
El-Hadidi M
影响因子：
5.2
作者：
Velazquez-Salinas L;Zarate S;Eberl S;Gladue DP;Novella I;Borca MV
通讯作者：
Borca MV
影响因子：
3.5
作者：
Matyasek, Roman;Kovarik, Ales
通讯作者：
Kovarik, Ales