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 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, 43.9% of the sequenced genomes present the E484K mutation, which was identified in three different lineages (P1, P2 and B.1.1.33) 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.

Mutation hotspots, geographical and temporal distribution of SARS-CoV-2 lineages in Brazil, February 2020-2021: insights and limitations from uneven sequencing efforts

“…Lineage P.1, emerged from the Brazilian state of Amazonas between November and December 2020, have accumulated a high number of non-synonymous mutations and is now dispersed across novel Brazilian regions, representing one of the most frequent lineages up to February 2021 (Faria et al 2021a; Naveca et al 2021). Second, the fact that the set of mutations shared by P.1, B.1.1.7 and B.1.351 seem to have arisen independently, as we have previously demonstrated with emergence of E484K in others Brazilian lineages (P.2, B.1.1.28 and B.1.1.33), is suggestive of convergent molecular evolution (Ferrareze et al 2021; Faria et al 2021b).…”

“…representing one of the most frequent lineages up to February 2021 (Faria et al 2021a;Naveca et al 2021) . Second, the fact that the set of mutations shared by P.1, B.1.1.7 and B.1.351 seem to have arisen independently, as we have previously demonstrated with emergence of E484K in others Brazilian lineages (P.2, B.1.1.28 and B.1.1.33), is suggestive of convergent molecular evolution (Ferrareze et al 2021;Faria et al 2021b) .…”

Phylogenomics and population genomics of SARS-CoV-2 in Mexico during the pre-vaccination stage reveals variants of interest B.1.1.28.4, B.1.1.222 or B.1.1.519 and B.1.243 with mutations in the Spike protein and the Nucleocapsid

“…With current data, however, it can only be concluded that P.3 is the result of an early P.2 entry followed by local evolution, warranting the follow-up of the behavior of E484K-containing variants in this region and throughout Mexico. In agreement with this, data available for Mexico and the rest of the world for the pre-vaccination stage suggests convergent evolution and spread of the virus containing mutation E484K (Lasek-Nesselquist, Lapierre, et al 2021;(Annavajhala et al 2021); (Ferrareze et al 2021), suggesting a major role of this amino acid change in higher transmission and/or viral replication and increased viral fitness. On the other hand, 20B/T478K.V1 can be undoubtedly classified as a VOI, with all the potential elements to become a VOC in Mexico and worldwide.…”

A single BNT162b2 mRNA dose elicits antibodies with Fc-mediated effector functions and boost pre-existing humoral and T cell responses

“…Among the mutations present in the B.1.1.7 strain, the N501Y is also present in many other circulating variants (B.1.351 and P.1) and increases the affinity for the ACE-2 receptor 15, 16 . The E484K mutation, is part of the South African B.1.351 variant and is now found in several SARS-CoV-2 genomes worldwide that spread rapidly 17 . Studies have shown that this mutation increases affinity of the S glycoprotein for ACE-2 18 and confers resistance to neutralization mediated by mAbs and plasma from naturally-infected and vaccinated individuals 19–22 .…”