Genomic Evidence of a Sars-Cov-2 Reinfection Case With E484K Spike Mutation in Brazil

Nonaka, Carolina Kymie Vasques; Franco, Marília Miranda; Gräf, Tiago; Mendes, A.; Aguiar, Renato Santana; Giovanetti, Marta; Souza, Bruno Solano de Freitas

doi:10.20944/preprints202101.0132.v1

Cited by 37 publications

(25 citation statements)

References 2 publications

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“…Importantly, B.1.351, P.1, and P.2 carry this substitution associated with escape from neutralizing antibodies (Baum et al, 2020;Greaney et al, 2020;Weisblum et al, 2020) . Recently, this mutation was also identified in a sample from a reinfected patient (Nonaka et al, 2021) .…”

Section: Introductionmentioning

confidence: 90%

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

Ferrareze

Franceschi

Mayer

et al. 2021

Preprint

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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.

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Section: Introductionmentioning

confidence: 90%

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

Ferrareze

Franceschi

Mayer

et al. 2021

Preprint

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“…The “South African” mutation, which includes three altered residues in the ACE2 binding site (K417N, E484K, and N501Y) spread extremely rapidly, becoming within weeks the dominant lineage in the Eastern Cape and Western Cape Provinces 7 . The “Brazilian” variant (P.1), independently fixing K417T, E484K, and N501Y mutations similar to the “South African” variant, is spreading rapidly from the Amazon region 8 . Another variant enhancing SARS-CoV-2 infectivity is S477N, which became dominant in many regions 9 .…”

Section: Introductionmentioning

confidence: 99%

“…Among the mutations selected and fixed in the yeast population during these initial steps of affinity maturation were three mutations that strongly emerged in clinical samples of SARS-CoV-2: S477N, E484K, and N501Y 7 8,9 . In addition, the yeast selection probed the most abundant naturally occurring variants in positions 490 and 493, which were lost in subsequent libraries of yeast selection (Table 1).…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 RBD in vitro evolution follows contagious mutation spread, yet generates an able infection inhibitor

Zahradník

Marciano

Shemesh

et al. 2021

Preprint

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SARS-CoV-2 is continually evolving, with more contagious mutations spreading rapidly. Using in vitro evolution to affinity maturate the receptor-binding domain (RBD) of the spike protein towards ACE2 resulted in the more contagious mutations, S477N, E484K, and N501Y, to be among the first selected, explaining the convergent evolution of the “European” (20E-EU1), “British” (501.V1),”South African” (501.V2), and ‘‘Brazilian” variants (501.V3). Plotting the binding affinity to ACE2 of all RBD mutations against their incidence in the population shows a strong correlation between the two. Further in vitro evolution enhancing binding by 600-fold provides guidelines towards potentially new evolving mutations with even higher infectivity. For example, Q498R epistatic to N501Y. Nevertheless, the high-affinity RBD is also an efficient drug, inhibiting SARS-CoV-2 infection. The 2.9Å Cryo-EM structure of the high-affinity complex, including all rapidly spreading mutations, provides a structural basis for future drug and vaccine development and for in silico evaluation of known antibodies.

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“…Crucially, E484K and other mutations at S/484 also frequently confer protection from neutralization by both convalescent sera 23 , vaccine elicited antibodies 17,[24][25][26] , and some monoclonal antibodies 23,26 . There is therefore increasing evidence that viruses carrying the E484K mutation (with or without 501Y) will be able to more frequently infect both previously infected 27 and vaccinated individuals 17,19,24 . Figure 1.…”

Section: Introductionmentioning

confidence: 99%

The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape

Martin

Weaver

Tegally

et al. 2021

Preprint

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The emergence and rapid rise in prevalence of three independent SARS-CoV-2 '501Y lineages', B.1.1.7, B.1.351 and P.1, in the last three months of 2020 has prompted renewed concerns about the evolutionarily capacity of SARS-CoV-2 to adapt to both rising population immunity and public health interventions such as vaccines and social distancing. Viruses giving rise to the different 501Y lineages have, presumably under intense natural selection following a shift in host environment, independently acquired multiple unique and convergent mutations. As a consequence all have gained epidemiological and immunological properties that will likely complicate the control of COVID-19. Here, by examining patterns of mutations that arose in SARS-CoV-2 genomes during the pandemic we find evidence of a major change in the selective forces acting on immunologically important SARS-CoV-2 genes (such as N and S) that likely coincided with the emergence of the 501Y lineages. In addition to involving continuing sequence diversification, we find evidence that a significant portion of the ongoing adaptive evolution of the 501Y lineages also involves further convergence between the lineages. Our findings highlight the importance of monitoring how members of these known 501Y lineages, and others still undiscovered, are convergently evolving similar strategies to ensure their persistence in the face of mounting infection and vaccine induced host immune recognition.

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Genomic Evidence of a Sars-Cov-2 Reinfection Case With E484K Spike Mutation in Brazil

Cited by 37 publications

References 2 publications

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

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

SARS-CoV-2 RBD in vitro evolution follows contagious mutation spread, yet generates an able infection inhibitor

The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape

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