Evolutionary analysis of the Delta and Delta Plus variants of the SARS-CoV-2 viruses

Abstract

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.

Spike Protein NTD mutation G142D in SARS-CoV-2 Delta VOC lineages is associated with frequent back mutations, increased viral loads, and immune evasion

“…However, our results suggest that reduced NAb binding to the NTD is one potential mechanism that deserves further investigation. The G142D mutation is located in close proximity to the alterations of E156G and DEL157-158 reported in all Delta VOC that is part of the N3 loop of the NTD 'super site' epitope recognized by NTD-directed NAbs and associated with reduced viral neutralization (28)(29)(30)(31)(32). Despite the well-known challenges of in-silico protein structure e prediction on the spike protein (e.g., preand post-fusion conformation, the impact of D614G and P681R mutations on furin cleavage structure, and native spike conformation vs various mutated spike protein and their effect on antibody binding to different NTD or RBD epitopes) all of our structural predictions modelled against different templates (native, NTD-or RBD antibody-bound) consistently predicted that G142D and T95I mutations contribute to significant changes in the NTD secondary structure, including the potential conversion of β -strand to α -helix around aa159-167 and 183-190 regions, hydrogen-bond changes due to altered residue charge at G142D, an enlarged pocket at T95I, and overall three dimensional NTD surface topography that is unfavorable to NAb binding in the presence of other Delta VOC signature mutations.…”

Severity, Pathogenicity and Transmissibility of Delta and Lambda Variants of SARS-CoV-2, Toxicity of Spike Protein and Possibilities for Future Prevention of COVID-19

“…There are two amino acid changes: L452R and T478K. Arginine is hydrophilic and polar in nature, and it can accelerate molecular transmission and infectivity in the mucosal environment [ 53 , 54 , 55 , 56 ]. However, the mechanism of interaction of arginine within the membrane is unknown.…”

Possible Link between Higher Transmissibility of Alpha, Kappa and Delta Variants of SARS-CoV-2 and Increased Structural Stability of Its Spike Protein and hACE2 Affinity

“…While this paper was ready for submission a new sub variant of B.1.617 was detected and named as Delta Plus . It contains same mutations as Delta variant and two other mutations-K417N and W258L in the spike glycoprotein [27]. Further, the B.1.618 (triple mutant), recently detected in the four Indian states (Maharashtra, Delhi, West Bengal and Chhattisgarh), has been characterized by the deletion of Tyr145 and His146 as well as E484K and D614G mutation in the spike protein (https://cov-lineages.org/) (accessed on 10 July 2021) [24].…”