Computer Simulations and Network-Based Profiling of Binding and Allosteric Interactions of SARS-CoV-2 Spike Variant Complexes and the Host Receptor: Dissecting the Mechanistic Effects of the Delta and Omicron Mutations.
PMID: 35457196
2022
International journal of molecular sciences
Introduction: Mutations present in the Omicron virus (S477N, E484K and N501Y) were preferentially selected by yeast surface display affinity maturation screen of RBD against ACE2.
Introduction: The comparison of binding affinity changes using a randomly mutated RBD screen displayed on the yeast surface for ACE2 binding showed the higher affinity for N501Y, E484K, S477N and Q498R, where the combination of Q498R and N501Y increased the binding affinity by 26-fold and adding the S477N mutation produced a 37-fold increase in the binding affinity.
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.
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
Immune evasion and chronological decrease in titer of neutralizing antibody against SARS-CoV-2 and its variants of concerns in COVID-19 patients.
Introduction: Even therapeutic monoclonal antibodies have been reported to have reduced or lost neutralizing ability against variants with the E484K mutation.
Result: In particular, the Beta and Gamma variants, which commonly have the E484K mutation, are shifted more than the red line in the center.
Dynamic Ca(2+) sensitivity stimulates the evolved SARS-CoV-2 spike strain-mediated membrane fusion for enhanced entry.
Result: We found that Beta fusion activity is ~15% lower compared to the Alpha strain, which could be due to the lower affinity of ACE2 for B1.351 than B.1.1.7 spike variant, due to additional mutation on B.1.351 variant (K417N and E484K), consistent with a previous report.
A screening strategy for identifying the dominant variant of SARS-COV-2 in the fifth peak of Kurdistan- Iran population using HRM and Probe-based RT-PCR assay.
PMID: 35271889
2022
Journal of virological methods
Method: Finally, a 598 PCR product containing L452R, E484K/Q, T478K, and D614G were synthesized, and then sequencing was done.
Method: Samples with the positive result for del69-70, E484K,
Result: In the CY5 channel, the wild type of E484Q and E484K were amplified in the 94 samples.
Result: Those samples with negative results for E484K, E484Q, and positive results for D614G, L452R were screened by HRM analysis plus T478K mutation specified for the Delta variant.
SARS_CoV_2 mutation literature information.
PMID: 
2022
International journal of molecular sciences
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