Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been rapidly evolving in the form of new variants. At least eleven known variants have been reported. The objective of this study was to delineate the differences in the mutational profile of Delta and Delta Plus variants. High-quality sequences (n = 1756) of Delta (B.1.617.2) and Delta Plus (AY.1 or B.1.617.2.1) variants were used to determine the prevalence of mutations (≥20 %) in the entire SARS-CoV-2 genome, their co-existence, and change in prevalence over a period of time. Structural analysis was conducted to get insights into the impact of mutations on antibody binding. A Sankey diagram was generated using phylogenetic analysis coupled with sequence-acquisition dates to infer the migration of the Delta Plus variant and its presence in the United States. The Delta Plus variant had a significant number of high-prevalence mutations (≥20 %) than in the Delta variant. Signature mutations in Spike (G142D, A222V, and T95I) existed at a more significant percentage in the Delta Plus variant than the Delta variant. Three mutations in Spike (K417N, V70F, and W258L) were exclusively present in the Delta Plus variant. A new mutation was identified in ORF1a (A1146T), which was only present in the Delta Plus variant with ~58 % prevalence. Furthermore, five key mutations (T95I, A222V, G142D, R158G, and K417N) were significantly more prevalent in the Delta Plus than in the Delta variant. Structural analyses revealed that mutations alter the sidechain conformation to weaken the interactions with antibodies. Delta Plus, which first emerged in India, reached the United States through England and Japan, followed by its spread to more than 20 the United States. Based on the results presented here, it is clear that the Delta and Delta Plus variants have unique mutation profiles, and the Delta Plus variant is not just a simple addition of K417N to the Delta variant. Highly correlated mutations may have emerged to keep the structural integrity of the virus.

严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 一直以新变种的形式迅速发展。至少有 11 种已知变体已被报道。本研究的目的是描述 Delta 和 Delta Plus 变体突变谱的差异。Delta (B.1.617.2) 和 Delta Plus（AY.1 或 B.1.617.2.1）变体的高质量序列 (n = 1756) 用于确定整个 SARS 中突变的流行率 (≥20%) -CoV-2 基因组、它们的共存以及一段时间内流行率的变化。进行结构分析以深入了解突变对抗体结合的影响。使用系统发育分析和序列采集日期生成桑基图，以推断 Delta Plus 变体的迁移及其在美国的存在。与 Delta 变体相比，Delta Plus 变体具有大量高流行突变 (≥20 %)。与 Delta 变体相比，Delta Plus 变体中尖峰的特征突变（G142D、A222V 和 T95I）的比例更高。Spike 中的三个突变（K417N、V70F 和 W258L）仅存在于 Delta Plus 变体中。在 ORF1a (A1146T) 中发现了一个新突变，该突变仅存在于 Delta Plus 变体中，患病率约为 58%。此外，五个关键突变（T95I、A222V、G142D、R158G 和 K417N）在 Delta Plus 中比在 Delta 变体中更为普遍。结构分析表明，突变会改变侧链构象，从而削弱与抗体的相互作用。最早出现在印度的Delta Plus，通过英国和日本到达美国，随后它传播到美国20多个。根据此处呈现的结果，很明显 Delta 和 Delta Plus 变体具有独特的突变谱，而 Delta Plus 变体不仅仅是在 Delta 变体中简单添加 K417N。可能已经出现高度相关的突变以保持病毒的结构完整性。