Figure Legends
FIGURE 1 : Geographic mapping of SARS-CoV-2 outbreak and its timeline of infection. A) SARS-CoV-2 variants of concern (VOC) as classified by the World Health Organization (WHO) and their first reported case represented on a world map. B) Global timeline of SARS-CoV-2 cases in thousands wherein weekly cases of SARS-CoV-2 VOC as obtained from the GISAID database from December 2019 to February 2022
FIGURE 2 : Schematic and structural annotation of SARS-CoV-2 spike glycoprotein variants. A) Mutations in each of the VOC- Alpha, Beta, Gamma, Delta and Omicron mapped on the SARS-CoV-2 spike gene. Substitutions are represented with yellow circles, deletions with red triangles and insertions with green triangles. Common mutations to multiple VOC have been connected through a standard line at that residue position. NTD: N-terminal domain, RBD: receptor binding domain, FP: fusion peptide, HR1: heptad repeat sequence 1, HR2: heptad repeat sequence 2, TMD: transmembrane domain. B) Mutations involved in each of the VOC of SARS-CoV-2 mapped on spike monomer. Mutated residues are depicted in red spherical representation and spike monomer shown in cartoon representation (PDB: 7df4). RBD in open conformation is depicted in orange and NTD in green. Epitopes that could not be marked in the PDB structure are marked with a dashed line and red spot at the location of the neighboring residues. V1176F mutation in the Gamma variant has not been shown since it belongs to the stalk region of spike which was was not available in the spike PDB structure of 7df4.
FIGURE 3 : Heat map of epitope residues of monoclonal antibodies. The epitope residues of the analysed mAbs are plotted as a heat map wherein the highest intensity colour is denoting the most frequent epitope site followed by the decreasing the colour gradient which depicts the less frequent epitope sites.
FIGURE 4 : Epitope mapping of monoclonal antibodies targeting SARS-CoV-2 spike. Mapping of epitopes of 74 experimentally validated mAbs against SARS-CoV-2 variants. The mutated epitope sites with respect to the Alpha, Beta, Gamma, Delta and Omicron variants are annotated as red, whereas the non-mutated sites are shown in green. The antibodies selected for the analysis are depicted on the y axis. The mutated epitope regions within the spike N-terminal domain are subdivided into N1, N2, N3 and N4 and the receptor-binding domain (RBD) is sub annotated as receptor binding motif (RBM) within RBD.
FIGURE 5 : Frequency of mutated epitopes and the amino acid changes at the epitope sites. A). The frequency of mutated epitopes among the 74 mAbs was analyzed based on the region of occurrence and is shown as colormap with different frequencies. B) The percentage of amino acid variations at the epitope site among all reported SARS-CoV-2 variants were mapped and shown as a bar graph with different colors depicting each amino acid change in a series. In addition, the mutated epitope regions within the spike protein are denoted structurally and are shown as residues labeled in red. In contrast, the complete epitope recognition sites are marked as yellow. Some of the epitope recognition sites (Amino acid residues- 12, 13,14,15,74,75,76,248,249,250,251,252,253,254) which are non-mutated couldn’t be marked as yellow as these where not depicted in the structure.