Genomic epidemiology of SARS-CoV-2 in Esteio, Rio Grande do Sul, Brazil

Abstract

Background Brazil is the third country most affected by Coronavirus disease-2019 (COVID-19), but viral evolution in municipality resolution is still poorly understood in Brazil and it is crucial to understand the epidemiology of viral spread. We aimed to track molecular evolution and spread of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Esteio (Southern Brazil) using phylogenetics and phylodynamics inferences from 21 new genomes in global and regional context. Importantly, the case fatality rate (CFR) in Esteio (3.26%) is slightly higher compared to the Rio Grande do Sul (RS) state (2.56%) and the entire Brazil (2.74%). Results We provided a comprehensive view of mutations from a representative sampling from May to October 2020, highlighting two frequent mutations in spike glycoprotein (D614G and V1176F), an emergent mutation (E484K) in spike Receptor Binding Domain (RBD) characteristic of the B.1.351 and P.1 lineages, and the adjacent replacement of 2 amino acids in Nucleocapsid phosphoprotein (R203K and G204R). E484K was found in two genomes from mid-October, which is the earliest description of this mutation in Southern Brazil. Lineages containing this substitution must be subject of intense surveillance due to its association with immune evasion. We also found two epidemiologically-related clusters, including one from patients of the same neighborhood. Phylogenetics and phylodynamics analysis demonstrates multiple introductions of the Brazilian most prevalent lineages (B.1.1.33 and B.1.1.248) and the establishment of Brazilian lineages ignited from the Southeast to other Brazilian regions. Conclusions Our data show the value of correlating clinical, epidemiological and genomic information for the understanding of viral evolution and its spatial distribution over time. This is of paramount importance to better inform policy making strategies to fight COVID-19.

Understanding the molecular interaction of SARS-CoV-2 spike mutants with ACE2 (angiotensin converting enzyme 2)

“…The conversion of negatively charged Glu484 to positively charged Lys484 in the E484K mutant, which we found to be the most stable complex according to the results of MM-PBSA analysis, has also been shown in another study to have profound effects on a highly flexible loop in the RBD (Franceschi, Caldana et al, 2021 ; Nelson et al, 2021 ). The comparison of the conformations of the wild-type spike-ACE2 complex with the E484K mutated spike-ACE2 complex ( Figure 5a ) shows clearly a conformational transition, where the spike protein is bent toward one of the ACE2 helices (residues 549–560).…”

“…Furthermore, vaccines manufactured by Novavax and Johnson & Johnson which have been tested in recent clinical trials were reported to be less effective against South African variants (B.1.351) harboring the E484K mutation than UK (B.1.1.7) and US (B.1.427 and B.1.429) lineages (Wise, 2021 ). Mechanistically, the E484K mutation in the flexible loop region of the SARS-CoV-2 receptor binding domain (RBD) causes the formation of novel favorable contacts in the RBD/ACE2 interface (Nelson et al, 2021 ) and more specifically, it ends up with a stronger ionic interaction between the residue GLU75 of ACE2 and the LYS484 of RBD (Franceschi, Caldana et al, 2021 ).…”

SARS-CoV-2 introduction and lineage dynamics across three epidemic peaks in Southern Brazil: massive spread of P.1

“…Besides these variants, Brazilian lineages B.1.1.28 and B.1.1.33, which emerged in São Paulo in late February 2020 ( Candido et al, 2020 ; Resende et al, 2021a ), were also detected among the first cases reported in RS. The dispersion pattern and demographical dynamics of these lineages showed that they were introduced by multiple events, and their spread occurred throughout Brazil by community transmission in early March, and also to other countries ( Candido et al, 2020 ; Franceschi et al, 2021 ; Mir et al, 2021 ; Resende et al, 2021a ).…”

Structural and functional insights into the spike protein mutations of emerging SARS-CoV-2 variants

“…However, the immunogenic significance of these regions is not well defined. Several mutations of the S2 domain include D769H, D950N [66,94,103,123,136,143,[147][148][149][150][151] (Fig. 10).…”