Table_1_Genome Sequencing Reveals a Mixed Picture of SARS-CoV-2 Variant of Concern Circulation in Eastern Uttar Pradesh, India.xlsx

Uttar Pradesh is the densely populated state of India and is the sixth highest COVID-19 affected state with 22,904 deaths recorded on November 12, 2021. Whole-genome sequencing (WGS) is being used as a potential approach to investigate genomic evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. In this study, a total of 87 SARS-CoV-2 genomes−49 genomes from the first wave (March 2020 to February 2021) and 38 genomes from the second wave (March 2021 to July 2021) from Eastern Uttar Pradesh (E-UP) were sequenced and analyzed to understand its evolutionary pattern and variants against publicaly available sequences. The complete genome analysis of SARS-CoV-2 during the first wave in E-UP largely reported transmission of G, GR, and GH clades with specific mutations. In contrast, variants of concerns (VOCs) such as Delta (71.0%) followed by Delta AY.1 (21.05%) and Kappa (7.9%) lineages belong to G clade with prominent signature amino acids were introduced in the second wave. Signature substitution at positions S:L452R, S:P681R, and S:D614G were commonly detected in the Delta, Delta AY.1, and Kappa variants whereas S:T19R and S:T478K were confined to Delta and Delta AY.1 variants only. Vaccine breakthrough infections showed unique mutational changes at position S:D574Y in the case of the Delta variant, whereas position S:T95 was conserved among Kappa variants compared to the Wuhan isolate. During the transition from the first to second waves, a shift in the predominant clade from GH to G clade was observed. The identified spike protein mutations in the SARS-CoV-2 genome could be used as the potential target for vaccine and drug development to combat the effects of the COVID-19 disease.

印度北方邦（Uttar Pradesh）是印度人口稠密的邦，同时也是该国第六大新冠疫情重灾区，截至2021年11月12日，该邦记录的新冠死亡病例达22904例。全基因组测序（whole-genome sequencing, WGS）是解析严重急性呼吸综合征冠状病毒2（severe acute respiratory syndrome coronavirus 2, SARS-CoV-2）基因组演化的有效手段。本研究对印度东部北方邦（Eastern Uttar Pradesh, E-UP）的87株SARS-CoV-2全基因组进行了测序与分析：其中49株采集自第一波疫情（2020年3月至2021年2月），其余38株采集自第二波疫情（2021年3月至2021年7月），旨在解析该地区病毒的演化模式与流行变异株，并与公开可用的序列开展比对分析。
第一波疫情期间，E-UP地区的SARS-CoV-2全基因组分析结果显示，该阶段主要流行G、GR、GH三类进化枝，且伴随特定突变。与之相对，第二波疫情中出现了属于G进化枝的关切变异株（Variants of Concern, VOCs），其中Delta株占比71.0%，其次为Delta AY.1株（21.05%）与Kappa株（7.9%），上述变异株均携带标志性氨基酸特征突变。
Delta、Delta AY.1与Kappa变异株均普遍存在S:L452R、S:P681R及S:D614G位点的标志性氨基酸替换突变；而S:T19R与S:T478K突变仅在Delta及Delta AY.1变异株中被检测到。针对Delta变异株的疫苗突破感染病例中，存在S:D574Y位点的独特突变；而相较于武汉原始分离株，Kappa变异株的S:T95位点保持保守。
在从第一波疫情向第二波疫情过渡的过程中，该地区病毒的优势进化枝由GH进化枝转变为G进化枝。本研究鉴定出的SARS-CoV-2刺突蛋白突变位点，可作为抗COVID-19疫苗与药物开发的潜在靶点，用于应对新冠疫情带来的危害。