E156G and Arg158, Phe-157/del mutation in NTD of spike protein in B.1.617.2 lineage of SARS-CoV-2 leads to immune evasion through antibody escape

Abstract

New emerging variants of SARS-CoV-2 remains a persistent threat with better immune escape mechanisms and higher transmissibility across the globe. B.1.617.2 (Delta) variant first emerged from Maharashtra, India in December, 2020. This variant is classified to be a major cause and concern of the recent peak of COVID-19 in India. Cellular entry of coronaviruses largely depends on binding of the viral spike (S) proteins to host receptors and priming by host cell proteases through the contact of the droplets containing pathogenic virus particles. Our research study, explore the genomic and structural basis of this variant through computational analysis, protein modelling and molecular dynamics simulations approach and identifies the mechanism through which it is probably more pathogenically evolved with higher transmissibility as compared to the wild-type. These findings reveal the significant difference in rigidity and reducing the flexibility within N-terminal domain (NTD) of the spike protein, hence prevailing case of antibody escape. The results of the present study demonstrate the fitness advantage to the new variant which further need to be critically examined though supportive experimental biology that might help devising better therapeutics and containment of SARS-CoV-2.

Defective ORF8 dimerization in SARS-CoV-2 delta variant leads to a better adaptive immune response due to abrogation of ORF8-MHC1 interaction

“…Reports on rigidization in NTD of spike had led to the antibody escape mechanism in this delta variant [9]. These studies are enough to display how lethal that this delta variant is in terms of transmittance, infectivity, and evading host immune responses.…”

COVID-19 pandemic: the delta variant, T-cell responses, and the efficacy of developing vaccines

“…Δ156–157 mutations help the variant escape immune recognition more efficiently due to changes in the configuration of the N-terminal domain. The flexibility of S-specific NTD of these new variants was decreased for the deletion mutation at the Arg158, and Phe157 with substitution mutation at E156G compared to the B.1.351 variant, which may affect the transmissibility [ 71 ]. A substitution mutation at P681R, situated at the furin cleavage site of S1/S2 junction, significantly increases the replication kinetics of the delta variant via higher fusogenic activity [ 72 , 73 ].…”

Interpretable and Predictive Deep Modeling of the SARS-CoV-2 Spike Protein Sequence

“…[169] Other mutations in Omicron sequences that greater neutralizing antibody activity are found at sites 156-158 with an E156G and F157/R158-δ substitution and deletion, which has been linked to a higher level of immune escape in Delta. [174]…”