A Potential SARS-CoV-2 Variant of Interest (VOI) Harboring Mutation E484K in the Spike Protein Was Identified within Lineage B.1.1.33 Circulating in Brazil

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Brazil was dominated by two lineages designated as B.1.1.28 and B.1.1.33. The two SARS-CoV-2 variants harboring mutations at the receptor-binding domain of the Spike (S) protein, designated as lineages P.1 and P.2, evolved from lineage B.1.1.28 and are rapidly spreading in Brazil. Lineage P.1 is considered a Variant of Concern (VOC) because of the presence of multiple mutations in the S protein (including K417T, E484K, N501Y), while lineage P.2 only harbors mutation S:E484K and is considered a Variant of Interest (VOI). On the other hand, epidemiologically relevant B.1.1.33 deriving lineages have not been described so far. Here we report the identification of a new SARS-CoV-2 VOI within lineage B.1.1.33 that also harbors mutation S:E484K and was detected in Brazil between November 2020 and February 2021. This VOI displayed four non-synonymous lineage-defining mutations (NSP3:A1711V, NSP6:F36L, S:E484K, and NS7b:E33A) and was designated as lineage N.9. The VOI N.9 probably emerged in August 2020 and has spread across different Brazilian states from the Southeast, South, North, and Northeast regions.

Keywords: Brazil; E484K; SARS-CoV-2; genomic epidemiology; variant of Interest.

Figure 1

Lineage N.9 evolutionary origin and spatial-temporal distribution. (a) Maximum likelihood (ML) phylogenetic tree of the B.1.1.33 whole-genome sequences from Brazil. The B.1.1.33 sequences with mutation S:E484K are represented by pink (VOI N.9) and green (B.1.1.33(E484K)) circles. The SH-aLRT support values are indicated in key nodes and branch lengths are drawn to scale with the left bar indicating nucleotide substitutions per site. (b) Geographic distribution of the VOI N.9 identified in Brazil. Brazilian states’ names follow the International Organization for Standardization (ISO) 3166-2 standard. (c) Correlation between the sampling date of B.1.1.33 sequences and their genetic distance from the root of the ML phylogenetic tree. Colors indicate the B.1.1.33 clade as indicated in (a). (d) Bayesian phylogeographic analysis of N.9 lineage. Tips and branches colors indicate the sampling state and the most probable inferred location of their descendent nodes, respectively, as indicated in the legend. Branch posterior probabilities are indicated in key nodes. Boxes highlight two N.9 subclades carrying additional mutations (indicated in each box). The tree was automatically rooted under the assumption of a strict molecular clock, and all horizontal branch lengths are time-scaled.