SARS-CoV-2 Omicron Mutation Is Faster than the Chase: Multiple Mutations on Spike/ACE2 Interaction Residues

Abstract

Recently, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (B.1.1.529) Omicron variant originated from South Africa in the middle of November 2021. SARS-CoV-2 is also called coronavirus disease 2019 (COVID-19) since SARS-CoV-2 is the causative agent of COVID-19. Several studies already suggested that the SARS-CoV-2 Omicron variant would be the fastest transmissible variant compared to the previous 10 SARS-CoV-2 variants of concern, interest, and alert. Few clinical studies reported the high transmissibility of the Omicron variant but there is insufficient time to perform actual experiments to prove it, since the spread is so fast. We analyzed the SARS-CoV-2 Omicron variant, which revealed a very high rate of mutation at amino acid residues that interact with angiostatin-converting enzyme 2. The mutation rate of COVID-19 is faster than what we prepared vaccine program, antibody therapy, lockdown, and quarantine against COVID-19 so far. Thus, it is necessary to find better strategies to overcome the current crisis of COVID-19 pandemic.

Keywords: COVID-19 Omicron; Mutation; Receptor binding motif (RBM); SARS-CoV-2; Spike (S) gene.

Figure 1. Comparison of SARS-CoV-2 WT to SARS-CoV-2 Omicron S protein. (A) The whole S protein sequence of SARS-CoV-2 Omicron was compared to that of SARS-CoV-2 WT. The mutated residue was highlighted by different colors such as yellow for amino acid change, blue for deletion, and green for insertion. RBD was highlighted by light pink and RBM was highlighted by light green. The signal sequence and transmembrane are in bold letters and underlined, it is also highlighted in gray. The absence of an asterisk at the bottom of alignment indicates a mutation site. (B) The RBD and RBM region was enlarged for further analysis. There are 15 mutations in RBD and 10 mutations in RBM of SARS-CoV-2 Omicron, whereas only 2 mutations (red bold letter) in RBM of SARS-CoV-2 Delta variant. (C) The alignment of Omicron and Delta S protein was compared to the ACE2 receptor interaction sites, which were reported by WT¹ (13), WT² (14), WT³ (18), and WT⁴ (9). The 21 receptor binding residues were indicated by the green highlight. The 6 common ACE2 interaction sites were marked by an asterisk on the top to indicate the location (9131418). The mutation residues in the RBM of Omicron and Delta were indicated by a red letter. The 7 receptor binding residues of Omicron in RBM were highlighted by blue color.

Figure 2. Geographical drawing of mutation sites in SARS-CoV-2 Omicron S gene. The S protein contains 16 subdomains that were shown by different colors with specific residues on the right. The S1 (R685) cleavage site was indicated at the top with a red arrow. The 15 mutations in RBD were indicated in red letters with a yellow highlight. The 10 mutations in RBM were indicated in red letters with a green highlight. Each amino acid change was illustrated at the bottom of the domain bar by geographical drawing. The 3 unique insertion sites were indicated by red letters in NTD.

SP, signal peptide; L, loop; SD, subdomain; FP, fusion peptide; CR, connected region; HR, heptad repeat; CH, central helix; BH, β-hairpin; TM, transmembrane domain; CT, cytosolic domain.