Amino acid variation analysis of surface spike glycoprotein at 614 in SARS-CoV-2 strains

Abstract

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to disperse globally with worrisome speed, identifying amino acid variations in the virus could help to understand the characteristics of it. Here, we studied 489 SARS-CoV-2 genomes obtained from 32 countries from the Nextstrain database and performed phylogenetic tree analysis by clade, country, and genotype of the surface spike glycoprotein (S protein) at site 614. We found that virus strains from mainland China were mostly distributed in Clade B and Clade undefined in the phylogenetic tree, with very few found in Clade A. In contrast, Clades A2 (one case) and A2a (112 cases) predominantly contained strains from European regions. Moreover, Clades A2 and A2a differed significantly from those of mainland China in age of infected population (P = 0.0071, mean age 40.24 to 46.66), although such differences did not exist between the US and mainland China. Further analysis demonstrated that the variation of the S protein at site 614 (QHD43416.1: p.614D>G) was a characteristic of stains in Clades A2 and A2a. Importantly, this variation was predicted to have neutral or benign effects on the function of the S protein. In addition, global quality estimates and 3D protein structures tended to be different between the two S proteins. In summary, we identified different genomic epidemiology among SARS-CoV-2 strains in different clades, especially in an amino acid variation of the S protein at 614, revealing potential viral genome divergence in SARS-CoV-2 strains.

Keywords: ACE2; COVID-19; Phylogenetic tree; SARS-CoV-2; Surface spike glycoprotein.

Figure 1

Different SARS-CoV-2 clades among countries in phylogenetic tree. (A) Phylogenetic tree of 489 SARS-CoV-2 genomes from Nextstrain, the cases were colored by countries. Branch labels were clades. (B) Clade Distribution of 489 SARS-CoV-2 genomes in world map from Nextstrain. Color by clades.

Figure 2

Amino acid variation of S protein at site 614 in Clade A2 and A2a SARS-Cov-2 strains. (A) Radial phylogenetic tree of 489 SARS-CoV-2 from Nextstrain, the cases were colored by the amino acid of S protein at site 614. Green: glutamic acid (D), yellow: glycine (G). Branch labels were clades. (B) Rectangular phylogenetic tree of 489 SARS-CoV-2 from Nextstrain, the cases were colored by the amino acid of S protein at site 614. Green: glutamic acid (D), yellow: glycine (G). Branch labels were the amino acid variation of SARS-Cov-2 proteins. (C) Diversity of S protein of SARS-Cov-2.

Figure 3

Variation in S protein at site 614 does not affect protein function. (A) Prediction results of the variation of S protein at 614. (B) Part multiple sequence alignment results, amino acids surrounding the variation position (614) were shown.

Figure 4

Protein modeling estimate of QHD43416.1 and QHD43416.1: p.614D > G. (A) Amino acids of QHD43416.1 and QHD43416.1: p.614D > G surrounding the site 614. (B) Protein modeling estimate results of QHD43416.1 and QHD43416.1: p.614D > G from SWISS-MODEL Server.

Figure 5

Three-dimensional (3D) protein structure models of QHD43416.1 and QHD43416.1: p.614D > G. (A) 3D protein structure of QHD43416.1 and QHD43416.1: p.614D > G performed by SWISS-MODEL Server. (B) The zooming-in region of site 614 of QHD43416.1 and QHD43416.1: p.614D > G performed by SWISS-MODEL Server.