Evaluation of immune evasion in SARS-CoV-2 Delta and Omicron variants

Emerging SARS-CoV-2 variants with higher transmissibility and immune escape remain a persistent threat across the globe. This is evident from the recent outbreaks of the Delta (B.1.617.2) and Omicron variants. These variants have originated from different continents and spread across the globe. In this study, we explored the genomic and structural basis of these variants for their lineage defining mutations of the spike protein through computational analysis, protein modeling, and molecular dynamic (MD) sim-ulations. We further experimentally validated the importance of these deletion mutants for their immune escape using a pseudovirus-based neutralization assay, and an antibody (4A8) that binds directly to the spike protein's NTD. Delta variant with the deletion and mutations in the NTD revealed a better rigidity and reduced flexibility as compared to the wild-type spike protein (Wuhan isolate). Furthermore, com-putational studies of 4A8 monoclonal antibody (mAb) revealed a reduced binding of Delta variant com-pared to the wild-type strain. Similarly, the MD simulation data and virus neutralization assays revealed that the Omicron also exhibits immune escape, as antigenic beta-sheets appear to be disrupted. The results of the present study demonstrate the higher possibility of immune escape and thereby achieved better fitness advantages by the Delta and Omicron variants, which warrants further demonstrations through experimental evidences. Our study, based on in-silico computational modelling, simulations, and pseudovirus-based neutralization assay, highlighted and identified the probable mechanism through which the Delta and Omicron variants are more pathogenically evolved with higher transmissibility as compared to the wild-type strain.(c) 2022 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creative-commons.org/licenses/by-nc-nd/4.0/).

Automated summary

Emerging SARS-CoV-2 variants, such as the Delta and Omicron variants, pose a persistent threat with higher transmissibility and immune escape. Computational analysis, protein modeling, molecular dynamic simulations, and experimental validation were used to explore the genomic and structural basis of these variants. The results demonstrate the potential mechanism through which the Delta and Omicron variants have evolved with higher transmissibility and immune escape compared to the wild-type strain.