Emerging SARS-CoV-2 variants: Why, how, and what's next?

Abstract

The emergence of the SARS-CoV-2 Omicron variant poses a striking threat to human society. More than 30 mutations in the Spike protein of the Omicron variant severely compromised the protective immunity elicited by either vaccination or prior infection. The persistent viral evolutionary trajectory generates Omicron-associated lineages, such as BA.1 and BA.2. Moreover, the virus recombination upon Delta and Omicron co-infections has been reported lately, although the impact remains to be assessed. This minireview summarizes the characteristics, evolution and mutation control, and immune evasion mechanisms of SARS-CoV-2 variants, which will be helpful for the in-depth understanding of the SARS-CoV-2 variants and policy-making related to COVID-19 pandemic control.

Keywords: Deltacron; Mutation rate; Mutations in the Spike; Omicron; SARS-CoV-2 variants.

Fig. 1

The mutation site in the genome of five variants of concern (Alpha, Beta, Gamma, Delta, and Omicron) and the newly found recombinedDelta-Omicron(EPI_ISL_10819657). Based on sequences from GISAID. ORF, open reading frame; S, Spike protein; N, nucleocapsid.

Fig. 2

Partial key sites in the Spike ofSARS-CoV-2and theSARS-CoV-2Spike trimer (WT) complexed with hACE2. The key sites with mutation are in red, and the highly conserved key sites are in black. The interface of the hACE2 and Spike from indicated variants was at the right panel of (B). Green, hACE2; blue, RBM; cyans, magenta, and yellow represent the indicated monomer of Spike. This figure is based on the structure data from the Protein Data Bank (accession code: 7DF4 (Xu et al., 2021), 7W98 (Wang et al., 2022a), and 7WPA (Yin et al., 2022)) NTD, N-terminal domain; RBD, receptor-binding domain; RBM, receptor-binding motif; FP, fusion peptide; HR, heptad repeat.

Fig. 3

An in trans backtracking model for proofreading (Yan et al., 2021b).