Omicron SARS-CoV-2 variant: Unique features and their impact on pre-existing antibodies

Abstract

Severe Acute Respiratory Coronavirus (SARS-CoV-2) has been emerging in the form of different variants since its first emergence in early December 2019. A new Variant of Concern (VOC) named the Omicron variant (B.1.1.529) was reported recently. This variant has a large number of mutations in the S protein. To date, there exists a limited information on the Omicron variant. Here we present the analyses of mutation distribution, the evolutionary relationship of Omicron with previous variants, and probable structural impact of mutations on antibody binding. Our analyses show the presence of 46 high prevalence mutations specific to Omicron. Twenty-three of these are localized within the spike (S) protein and the rest localized to the other 3 structural proteins of the virus, the envelope (E), membrane (M), and nucleocapsid (N). Phylogenetic analysis showed that the Omicron is closely related to the Gamma (P.1) variant. The structural analyses showed that several mutations are localized to the region of the S protein that is the major target of antibodies, suggesting that the mutations in the Omicron variant may affect the binding affinities of antibodies to the S protein.

Keywords: B.1.1.529; COVID-19; Omicron variant; SARS-CoV-2; Variants.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Figures

Fig. 1

Relative abundance (RA) of signature Omicron variant mutations.Panel A shows the RA of Spike signature mutations and high prevalent mutations in OFR1a and ORF1b. Panel B shows the RA of Omicron variant mutations in ORF1a and ORF1b and signature mutations in structural proteins E, M, and N. Please note ORF1b:P314L corresponds to nsp12 mutation nsp12:P323L. Panel C shows the phylogenetic relationship among different SARS-CoV-2 variants. The GISAID identification numbers for the sequences used in Panel B are as below. 1_Alpha to 10_Alpha: EPI_ISL_5803029, EPI_ISL_6000214, EPI_ISL_6026865, EPI_ISL_6027306, EPI_ISL_6141708, EPI_ISL_6227805, EPI_ISL_6229383, EPI_ISL_6251101, EPI_ISL_6383583, EPI_ISL_675143; 1_Beta1 to 10_Beta: EPI_ISL_5053750, EPI_ISL_5274500, EPI_ISL_5430264, EPI_ISL_5515861, EPI_ISL_5524663, EPI_ISL_6422293, EPI_ISL_6699711, EPI_ISL_6751445, EPI_ISL_6774033, EPI_ISL_6774035; 1_Gamma to 10_Gamma: EPI_ISL_6121588, EPI_ISL_6121598, EPI_ISL_6121603, EPI_ISL_6569634, EPI_ISL_6689781, EPI_ISL_6689782, EPI_ISL_6689786, EPI_ISL_6689787, EPI_ISL_6689788, EPI_ISL_6689789; 1_Delta to 10_Delta: EPI_ISL_6739692, EPI_ISL_6739693, EPI_ISL_6761790, EPI_ISL_6763188, EPI_ISL_6769723, EPI_ISL_6772657, EPI_ISL_6775864, EPI_ISL_6775870, EPI_ISL_6795204, EPI_ISL_6809412; 1_ Mu to 10_Mu: EPI_ISL_6526278, EPI_ISL_6526285, EPI_ISL_6569586, EPI_ISL_6569593, EPI_ISL_6569599, EPI_ISL_6569609, EPI_ISL_6569625, EPI_ISL_6569673, EPI_ISL_6675615, EPI_ISL_6675624, and 1_Omicron to 10_ Omicron: EPI_ISL_6752026, EPI_ISL_6774086, EPI_ISL_6699747, EPI_ISL_6699744, EPI_ISL_6699751, EPI_ISL_6752027, EPI_ISL_6699728, EPI_ISL_6699764, EPI_ISL_6699734, EPI_ISL_6698790.

Fig. 2

Distribution of amino acid residue position at Spike/ACE or Spike/antibody interface.Panel A shows the distribution of amino acid residues mutated in the Omicron variant in the complex formed between S-RBD encoded by BNT162b1 and ACE2. This figure has been generated by PDB entry 7L7F. Panel B shows the position of residues at the interface of S-RBD and antibody IGHV3-53, where the mutations in Omicron variant have been identified. The S protein is rendered in green ribbons, whereas the antibody is rendered in orange and light-blue ribbons. The amino acid residues representing the mutation sites in the Omicron variant are rendered as balls and sticks. Panel C shows the interaction Y145 of S protein with antibody (1–87) residues A97 and V98. A deletion mutation (as seen in Omicron variant) will abrogate these interactions. This figure also shows some residue positions in S protein where the mutations in Delta and Delta Plus variants are present. Figures for Panel D and E were generated from PDB entries 7JMP and 7L2D, respectively. In both panels, the atoms of S protein residues are colored as green – carbons, blue–nitrogens, and red – oxygens. Atoms of antibodies are colored as orange – carbons, blue – nitrogens, and red – oxygens.