SARS-CoV-2 Delta (B.1.617.2) Variant: A Unique T478K Mutation in Receptor Binding Motif (RBM) of Spike Gene

Abstract

Over two hundred twenty-eight million cases of coronavirus disease 2019 (COVID-19) in the world have been reported until the 21^st of September 2021 after the first rise in December 2019. The virus caused the disease called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Over 4 million deaths blame COVID-19 during the last one year and 8 months in the world. Currently, four SARS-CoV-2 variants of concern are mainly focused by pandemic studies with limited experiments to translate the infectivity and pathogenicity of each variant. The SARS-CoV-2 α, β, γ, and δ variant of concern was originated from United Kingdom, South Africa, Brazil/Japan, and India, respectively. The classification of SARS-CoV-2 variant is based on the mutation in spike (S) gene on the envelop of SARS-CoV-2. This review describes four SARS-CoV-2 α, β, γ, and δ variants of concern including SARS-CoV-2 ε, ζ, η, ι, κ, and B.1.617.3 variants of interest and alert. Recently, SARS-CoV-2 δ variant prevails over different countries that have 3 unique mutation sites: E156del/R158G in the N-terminal domain and T478K in a crucial receptor binding domain. A particular mutation in the functional domain of the S gene is probably associated with the infectivity and pathogenesis of the SARS-CoV-2 variant.

Keywords: COVID-19 delta; Receptor binding motif (RBM); SARS-CoV-2; Spike gene; T478K.

Figure 1. Schematic drawing of 16 subdomains in spike glycoprotein of SARS-CoV-2. The spike glycoprotein is composed of 16 subdomains. The S1 region (R685) cleavage site is indicated at the top. SARS-CoV-2 α, β, γ, and δ variant mutation sites were indicated by specific amino acid substitution. The common D614G in all ten variant (Table 1) was indicated by bold blue letter. (A) SARS-CoV-2 α variant has 13 mutation sites were listed at the bottom. (B) SARS-CoV-2 β variant has 10 mutation sites were listed at the bottom. (C) SARS-CoV-2 γ variant has 11 mutation sites were listed at the bottom. (D) SARS-CoV-2 δ variant has 15 mutation sites were listed at the bottom. A unique residue of SARS-CoV-2 δ variant was indicated with a large bolded red letter. The 16 subdomains of spike protein were illustrated by different colors with specific residues on the right. SP, signal peptide; NTD, N-terminal domain; 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.

Figure 2. The occurrence of ten SARS-CoV-2 variants located in the world map. (A) The world map showed the origin of the ten SARS-CoV-2 variants although SARS-CoV-2 originated from Wuhan China. (B) The spread of SARS-CoV-2 δ variant in 6 continents including other nine SARS-CoV-2 variants.

Figure 3. Mutation sites in the RBM of ten SARS-CoV-2 variants. The alignment of spike RBM in the ten SARS-CoV-2 variant was directly compared to the receptor binding residues that were reported by WT¹ (16), WT² (17), WT³ (27), and WT⁴ (12). The twenty-one receptor interaction residues in WT¹–WT⁴ were highlighted by green color in upper 4 lines. The six common ACE2 interaction sites were indicated with asterisk (*) on the top (12161727). The mutation sites of four SARS-CoV-2 α, β, γ, and δ variants of concern and six SARS-CoV-2 ε, ζ, η, ι, κ, and B.1.617.3 variants of interest and alert were indicated by red letter. The unique T478K mutation site of δ variant was indicated by a large red font with yellow highlight.