SARS-CoV-2: Searching for the Missing Variants

Abstract

Structural and phylogenetic analysis of the spike glycoprotein highlighted that the last variants, annotated as omicron, have about 30 mutations compared to the initial version reported in China, while the delta variant, supposed to be the omicron ancestor, shows only 7 mutations. Moreover, the five omicron variants were isolated between November 2021 and January 2022, and the last variant BA.2.75, unofficially named centaurus, was isolated in May 2022. It appears that, since the isolation of the delta variant (October 2020) to the omicron BA.1 (November 2021), there was an interval of one year, whereas the five omicron variants were isolated in three months, and after a successive four months period, the BA.2.75 variant was isolated. So, what is the temporal and phylogenetic correlation among all these variants? The analysis of common mutations among delta and the omicron variants revealed: (i) a phylogenetic correlation among these variants; (ii) the existence of BA.1 and BA.2 omicron variants a few months before being isolated; (iii) at least three possible intermediate variants during the evolution of omicron; (iv) the evolution of the BA.2.12.1, BA.4 and BA.5 variants from omicron BA.2; (v) the centaurus variant evolution from omicron BA.2.12.1.

Keywords: SARS-CoV-2; SARS-CoV-2 variants; phylogenetic analysis.

Figure 1

Schematic representation of the omicron variants evolution starting from delta. The common mutations are reported at the overlap among the variants. The mutations present in all the omicron variants are S373P, K417N, N440K, S477N, T478K, E484A, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H and N969K, and T478K and D614G derived from delta, indicated by the yellow arrow. The unique mutations of each variant are reported outside the overlap among the variants.

Figure 2

Phylogenetic lineage of the omicron variants starting from wild type version and the delta variant. Intermediates 1, 2 and 3 are three missing variants. Intermediate 1 has common mutations between delta and Intermediate 2. Intermediate 2 has the common mutations of all the omicron variants. Intermediate 3 has the common mutation between omicron BA.4 and BA.5.