Gopalan Vidya, Chandran Aswathi, Arumugam Kishore, Sundaram Monisha, Velladurai Selvakumar, Govindan Karthikeyan, Azhagesan Nivetha, Jeyavel Padmapriya, Dhandapani Prabu, Sivasubramanian Srinivasan, Kitambi Satish Srinivas
Department of Virology, King Institute of Preventive Medicine and Research, Chennai, Tamil Nadu, India.
Department of Microbiology, Dr. ALM Post Graduate, Institute of Basic Medical Sciences, University of Madras, Chennai, Tamil Nadu, India.
J Glob Infect Dis. 2023 May 17;15(2):43-51. doi: 10.4103/jgid.jgid_178_22. eCollection 2023 Apr-Jun.
Prolonged COVID-19 pandemic accelerates the emergence and transmissibility of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants through the accumulation of adaptive mutations. Particularly, adaptive mutations in spike (S) protein of SARS-CoV-2 leads to increased viral infectivity, severe morbidity and mortality, and immune evasion. This study focuses on the phylodynamic distribution of SARS-CoV-2 variants during the year 2021 in India besides analyzing the functional significance of mutations in S-protein of SARS-CoV-2 variants.
Whole genome of SARS-CoV-2 sequences ( = 87957) from the various parts of India over the period of January to December 2021 was retrieved from Global Initiative on Sharing All Influenza Data. All the S-protein sequences were subjected to clade analysis, variant calling, protein stability, immune escape potential, structural divergence, Furin cleavage efficiency, and phylogenetic analysis using various tools.
Delta variant belonging to 21A, 21I, and 21J clades was found to be predominant throughout the year 2021 though many variants were also present. A total of 4639 amino acid mutations were found in S-protein. D614G was the most predominant mutation in the S-protein followed by P681R, L452R, T19R, T478K, and D950N. The highest number of mutations was found in the N-terminal domain of S-protein. Mutations in the crucial sites of S-protein impacting pathogenicity, immunogenicity, and fusogenicity were identified. Intralineage diversity analysis showed that certain variants of SARS-CoV-2 possess high diversification.
The study has disclosed the distribution of various variants including the Delta, the predominant variant, in India throughout the year 2021. The study has identified mutations in S-protein of each SARS-CoV-2 variant that can significantly impact the virulence, immune evasion, increased transmissibility, high morbidity, and mortality. In addition, it is found that mutations acquired during each viral replication cycle introduce new sub-lineages as studied by intralineage diversity analysis.
长期的新冠疫情通过适应性突变的积累加速了严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体的出现和传播。特别是，SARS-CoV-2刺突（S）蛋白中的适应性突变导致病毒传染性增加、严重发病率和死亡率上升以及免疫逃逸。本研究除了分析SARS-CoV-2变体S蛋白中突变的功能意义外，还聚焦于2021年印度SARS-CoV-2变体的系统动力学分布。
从全球共享流感数据倡议组织获取了2021年1月至12月期间印度各地的SARS-CoV-2序列（n = 87957）的全基因组。使用各种工具对所有S蛋白序列进行进化枝分析、变异体鉴定、蛋白质稳定性、免疫逃逸潜力、结构差异、弗林蛋白酶切割效率和系统发育分析。
尽管也存在许多变体，但属于21A、21I和21J进化枝的德尔塔变体在2021年全年都占主导地位。在S蛋白中总共发现了4639个氨基酸突变。D614G是S蛋白中最主要的突变，其次是P681R、L452R、T19R、T478K和D950N。在S蛋白的N端结构域中发现的突变数量最多。鉴定出了S蛋白关键位点上影响致病性、免疫原性和融合性的突变。谱系内多样性分析表明，某些SARS-CoV-2变体具有高度多样性。
该研究揭示了包括占主导地位的德尔塔变体在内的各种变体在2021年全年在印度的分布情况。该研究确定了每个SARS-CoV-2变体S蛋白中的突变，这些突变可显著影响毒力、免疫逃逸、传播性增加、高发病率和死亡率。此外，通过谱系内多样性分析发现，在每个病毒复制周期中获得的突变会引入新的亚谱系。
