E484K as an innovative phylogenetic event for viral evolution: Genomic analysis of the E484K spike mutation in SARS-CoV-2 lineages from Brazil

Abstract

The COVID-19 pandemic caused by SARS-CoV-2 has affected millions of people since its beginning in 2019. The propagation of new lineages and the discovery of key mechanisms adopted by the virus to overlap the immune system are central topics for the entire public health policies, research and disease management. Since the second semester of 2020, the mutation E484K has been progressively found in the Brazilian territory, composing different lineages over time. It brought multiple concerns related to the risk of reinfection and the effectiveness of new preventive and treatment strategies due to the possibility of escaping from neutralizing antibodies. To better characterize the current scenario we performed genomic and phylogenetic analyses of the E484K mutated genomes sequenced from Brazilian samples in 2020. From October 2020, more than 40% of the sequenced genomes present the E484K mutation, which was identified in three different lineages (P.1, P.2 and B.1.1.33 - posteriorly renamed as N.9) in four Brazilian regions. We also evaluated the presence of E484K associated mutations and identified selective pressures acting on the spike protein, leading us to some insights about adaptive and purifying selection driving the virus evolution.

Keywords: COVID-19; E484K; Infectious diseases; Severe acute respiratory syndrome coronavirus 2; Viral evolution.

Graphical abstract

Fig. 1

Histogram of frequent mutations observed in the Brazilian SARS-CoV-2 genomes harboring E484K mutation. Red labels above the bars indicate absolute nucleotide position and the blue labels indicate effects of these mutations in the corresponding proteins. As P.1 has only 19 genomes represented and multiple mutations, only main mutations of concern were highlighted. UTR: Untranslated region; Syn: Synonymous substitution; del: deletion; ORF: Open Reading Frame; Nsp: Non-structural protein; S: Spike; E: Envelope; M: Membrane; N: Nucleocapsid.

Fig. 2

Bayesian phylogenetic inference of the 134 Brazilian E484K mutated genomes. Tips were colored by Brazilian state and the reference genome NC_045512.2 is represented in black. The branches were highlighted by lineage: green (B.1.1.33), light green (N.9), beige (B.1.1.28), light red (P.2) and blue (P.1). Mutations occurring in all analyzed genomes for each lineage were described next to the respective nodes. The asterisks indicate the SARS-CoV-2 genomes sequenced by our research group.

Fig. 3

Distribution of genomes harboring E484K mutation across different lineages (A) and Brazilian states (B) from October to December 2020.

Fig. 4

Monthly presence of the E484K mutation considering worldwide available data (A) and Brazilian genomes (B). For clarity, the number of genomes in (A) are represented in log10 scale.