SARS-CoV-2 infections in mRNA vaccinated individuals are biased for viruses encoding spike E484K and associated with reduced infectious virus loads that correlate with respiratory antiviral IgG levels.
Abstract: The predominant virus variant was the Alpha (B.1.1.7), however a significant association between lineage B.1.526 and amino acid change S: E484K with positives after vaccination was noted.
Result: Spike substitution analysis showed that the S: E484K was associated with genomes of the vaccinated group (p = 0.0032.
Discussion: Genomic analysis revealed a statistically significant increased representation of lineage B.1.526 as well as the Spike amino acid change S: E484K in genomes from the vaccinated group.
Discussion: Our data showed a significant association of S: E484K with positives after full vaccination using a well-controlled analysis and a relatively large sample size in a time when t
Characteristic analysis of Omicron-included SARS-CoV-2 variants of concern.
Result: The scores of E484K and N501Y are also relatively close, indicating that these mutations do not affect the epitope of the spike protein of the Beta strain (Figure 2E).
Discussion: For example, E484K mutations are currently known to affect the neutralization of serum or monoclonal antibodies (mAb) during the recovery period.
Antigenicity comparison of SARS-CoV-2 Omicron sublineages with other variants contained multiple mutations in RBD.
Discussion: Similarly, the strong neutralization protection of Lambda spike-immunized sera against B.1.630 and B.1.640.1 may be due to the presence of L452Q (B.1.630 containing L452R mutation) and F490S (B.1.640.1 containing F490R mutation but not E484K mutation) in the Lambda immunogen.
Discussion: Surprisingly, these four groups of sera also had poor neutralizing activity against C.1.2 and B.1.640.2, which may be caused by E484K mutation.
Discussion: The immunogenicity of Beta, Gamma, and Mu were similar, probably because these three immunogens all contained E484K and N501Y mutations (Figure S1).
Role of the Microbiome in the Pathogenesis of COVID-19.
PMID: 35433495
2022
Frontiers in cellular and infection microbiology
Conclusion: The neutralization resistance occurred due to E484K and N501Y mutations in the RBD of the spike.
Conclusion: Till now, five variants designated as variants of concern (VOCs) by ECDC have been detected, namely, the Alpha (B.1.1.7), Alpha+E484K (B.1.1.7+ Introduction: An initial deletion of F140 (deletion of phenylalanine at position 140) in the N-terminal domain (NTD) N3 loop of spike protein in 36% virions and subsequently an E484K substitution in the receptor-binding domain (RBD) and later an insertion in the NTD N5 loop containing a new glycan sequence were observed on simultaneous passage and RNA sequencing.
Development of antibody resistance in emerging mutant strains of SARS CoV-2: Impediment for COVID-19 vaccines.
Abstract: Lower than expected inhibitory activity of antibodies was reported against viruses with E484K Spike mutation, including B.1.1.7 (UK), P.1 (Brazil), B.1.351 (South African), and new Omicron variant (B.1.1.529) with E484A mutation.
Molecular Dynamics and MM-PBSA Analysis of the SARS-CoV-2 Gamma Variant in Complex with the hACE-2 Receptor.
Result: A closer inspection on the specific contributions of each of the three mutations in the RBM indicate that the highest binding energy contribution variation was observed in the E484K mutation (Table 2).
Result: As expected, the G linked to mutations K417T (G = 2.32 kcal/mol) and E484K (G = -3.32 kcal/mol) has a compensatory character.
Result: In the literature, it has been suggested that the E484K mutation confers to the virus the ability to evade the humoral immune system rather than imprinting a higher affinity for the receptor.
Result: Regarding the E484K mutation, the results suggest a long-range electrostatic stabilization rather than a residue specific interaction.
Result: Specifically, in the gamma variant, a loss of affinity due to the E484K
Inhibitor screening using microarray identifies the high capacity of neutralizing antibodies to Spike variants in SARS-CoV-2 infection and vaccination.
Introduction: Similar results were obtained when testing a B.1.1.7 variant with an additional E484K mutation.
Introduction: The B.1.351 and P.1 variants contain three RBD mutations at E484K, N501Y, and K417N or
Discussion: Moreover, resistance could be enhanced with the combination of E484K/K417N mutations.
Discussion: The results are consistent to our data using monoclonal and polyclonal antibodies and the serum from convalescent patients and vaccinees (Figure 4 and 5), suggesting that N501Y/E484K/K417N mutations improve the inhibition of S-ACE2 interactions.
Multiple SARS-CoV-2 Variants Exhibit Variable Target Cell Infectivity and Ability to Evade Antibody Neutralization.
Discussion: The immune escape of some variants against LY-CoV555 may be related to the E484K/A mutation.
SARS-CoV-2 variants of concern alpha, beta, gamma and delta have extended ACE2 receptor host ranges.
PMID: 35377298
2022
The Journal of general virology
Abstract: All four VOCs were able to overcome a previous restriction for mouse ACE2, with demonstrable differences also seen for individual VOCs with rat, ferret or civet ACE2 receptors, changes that we subsequently attributed to N501Y and E484K substitutions within the spike RBD.
Emergence and phenotypic characterization of the global SARS-CoV-2 C.1.2 lineage.
Method: The SARS-CoV-2 Wuhan-1 spike, cloned into pCDNA3.1, was mutated using the QuikChange Lightning Site-Directed Mutagenesis kit (Agilent Technologies) and NEBuilder HiFi DNA Assembly Master Mix (NEB) to include D614G (wild-type) or lineage defining mutations for Beta (L18F, D80A, D215G, 241-243del, K417N, E484K, N501Y, D614G<
Figure: Key mutations known/predicted to influence neutralization sensitivity (C136F and P25L, Delta144Y, Delta242L/243A, and E484K), or furin cleavage (H655Y and N679K) are indicated.
SARS_CoV_2 mutation literature information.
PMID: 
2022
Journal of clinical virology
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