Computational Investigation of Selected Spike Protein Mutations in SARS-CoV-2: Delta, Omicron, and Some Circulating Subvariants

Abstract

Among the multiple SARS-CoV-2 variants recently reported, the Delta variant has generated the most perilous and widespread effects. Another variant, Omicron, has been identified specifically for its high transmissibility. Omicron contains numerous spike (S) protein mutations and numbers much larger than those of its predecessor variants. In this report, the author has discussed some essential structural aspects and time-based structure changes of a selected set of spike protein mutations within the Delta and Omicron variants. The expected impact of multiple point mutations within the spike protein's receptor-binding domain (RBD) and S1 of these variants are examined. Additionally, the RBDs of the more recently emerged subvariants BA.4, BA.5, and BA.2.12.1 are discussed. Within the latter group, BA.5 represents the most prevalent form of SARS-CoV-2 globally until recently. This computational work also briefly explores the temporal mutation profile for the currently circulating variants of interest (VOIs), variants under monitoring (VUMs), and variants being monitored (VBMs) including XBB.1.5, BQ.1, BA.2.75, CH.1.1, XBB, XBF, EG.5 (or Eris), and BA.2.86 (or Pirola). It is expected that these structural data can facilitate the tasks of identifying drug targets and neutralizing antibodies for the evolving variants/subvariants of SARS-CoV-2.

Keywords: COVID-19 infection; Omicron subvariants; SARS-CoV-2; infectious immunology; spike protein; structural immunology; variant being monitored; virus structure.

Figure 1

(A–E) Ribbon diagram of SARS-CoV-2 variants and subvariants with selected receptor-binding domain (RBD) mutations. These variants are based on the 6M0J structure. Displayed are the RBDs of (A) Delta variant; (B) Omicron variant; (C) Omicron BA.2 subvariant; (D) Omicron BA.4/BA.5 subvariant; (E) Omicron BA.2.12.1 subvariant with selected RBD mutations. (F–H) Ribbon diagram of SARS-CoV-2 variants and subvariants with selected S1 mutations. The mutant structures are based on model S1. Displayed are the S1 of the (F) Delta variant, (G) Omicron variant, and the (H) subvariant BA.2 with selected S1 mutations.

Figure 2

(A) The typical all-atom root-mean-square deviation (RMSD) plots of wt and different SARS-CoV-2 variants and subvariants with selected RBD mutations. These variants and subvariants are based on the 6M0J structure. (B) The average RMSD values of wt RBD, Delta, Omicron variants, and BA.2 subvariant with selected RBD mutations. These values are extracted from (A). (C) The typical RMSD plots of RBD mutations within different SARS-CoV-2 variants and subvariants. (D) The average RMSD values of SARS-CoV-2 mutations within different variants and subvariants. These values are extracted from (C). In all cases, the all-atom RMSD values are considered.

Figure 3

(A) The typical all-atom RMSD plots of wt and recently emerged SARS-CoV-2 Omicron subvariants with selected RBD mutations. These subvariants are based on the 6M0J structure. (B) The average RMSD values of wt RBD, subvariants BA.4/BA.5 and BA.2.12.1 with selected RBD mutations. These values are extracted from (A). (C) The typical all-atom RMSD plots of RBD mutations within subvariants BA.4/BA.5 and BA.2.12.1. (D) The average RMSD values for SARS-CoV-2 RBD mutations within different subvariants. The average values are extracted from (C).

Figure 4

(A) The typical all-atom RMSD plots of wt and different SARS-CoV-2 variants and subvariants with selected S1 mutations. These variants and subvariants are based on the model structure of SARS-CoV-2 S1. (B) The average RMSD values of wt S1, the Delta and Omicron variants, and Omicron subvariant BA.2 with selected S1 mutations. These values were extracted from (A). (C) The typical RMSD plots of S1 mutations within different SARS-CoV-2 variants and subvariants. (D) The average RMSD values of SARS-CoV-2 S1 mutations within different variants/subvariants. The average RMSD values were extracted from (C).

Figure 5

Time-based secondary structure changes of SARS-CoV-2 mutant variants and subvariants. The vertical axis represents the mutated residues and the horizontal axis represents the simulation trajectory. (A–E) The SARS-CoV-2 RBDs of (A) Delta; (B) Omicron; (C) BA.2; (D) BA.4/BA.5; (E) BA.2.12.1 with selected RBD mutations. These secondary structural changes were recorded for 25 ns. (F) Color code explanation of proteins’ secondary structures. These are the default color codes generated by the Visual Molecular Dynamics (VMD) graphical user window (GUI).

Figure 6

Average solvent-accessible surface area (SASA) values of SARS-CoV-2 RBD mutations observed predominantly in variants and subvariants (A) Delta; (B) Omicron; (C) BA.2; (D) BA.4/BA.5; (E) BA.2.12.1.