Abstract: In addition, three antibody clones retained in vitro blocking activity when the E484K spike protein mutant was used.
Method: To determine the binding EC50 of VNAR clones, high binding 96-well microplates (Greiner) were coated overnight at 4 C with 100 mul of S1, S1-RBD or HSA at 5 microg/ml and S1-RBD E484K and S1-RBD N501Y at 1 microg/ml.
Result: Binding of VNAR-hFc antibodies to S1-RBD
Result: Binding of these 10 VNAR-hFc antibodies was assessed against two key mutations in S1-RBD region, N501Y and E484K found in the newly emerged SARS-CoV-2 variants.
SARS-CoV-2 Virus-Host Interaction: Currently Available Structures and Implications of Variant Emergence on Infectivity and Immune Response.
PMID: 34639178
2021
International journal of molecular sciences
Discussion: Importantly, N501Y and E484K were present, emerged frequently in earlier stages and have already been found in emerging variants, suggesting some predicting potential for possible new variants.
Discussion: One of the defining characteristics of this variant is the high number of mutations, particularly in the spike protein, with three mutations specific to the RBD (K417T, E484K and N501Y), that lead to a 19-fold increase in affinity compared to the Wuhan strain.
Discussion: Some of the mutations present in the optimized RBD are also present in new variants as critical mutations in variants of concern, appearing often and early in the mutagenesis process, particularly mutations PMID: 34642465
2021
Scientific reports
Figure: Main interactions involving the S-RBDCoV-2 E484K (A), Q3493R (B), S494R (C), and L452R (D) mutants at the interface with the LY-CoV555 (bamlanivimab) mAb as obtained from the relevant equilibrated MD simulations.
Discussion: 2A,B, Table S2), we considered all possible mutations actually reported at this position in circulating viral variants (i.e., E484A/D/G/K/Q/R/V), and found that all these amino acid variations should confer strong escaping ability to bamlanivimab.
Discussion: And this, in turn, support the view that vaccination elicits a natural infection-like antibody response, and that spike variants like E484K may spread as antigenic evolutions of SARS-Co
The evolution of the mechanisms of SARS-CoV-2 evolution revealing vaccine-resistant mutations in Europe and America.
3Introduction: As mentioned in Ref., RBD mutations such as E484K/A, Y489H, Q493K, and N501Y found in late-stage evolved S variants ""confer resistance to a common class of SARS-CoV-2 neutralizing antibodies"", which suggests the viral evolution is also regulated by vaccine-resistant mutations."
Introduction: Later on, we have provided a list of most likely vaccine escape RBD mutations with high frequency, including S494P, Q493L, K417N, F490S, F486L, R403K, E484K, L4
Shared Mutations in Emerging SARS-CoV-2 Circulating Variants May Lead to Reverse Transcription-PCR (RT-PCR)-Based Misidentification of B.1.351 and P.1 Variants of Concern.
Introduction: For the remaining cases, for which the RT-PCR-based prescreening did not detect the E484K/N501Y mutations, three (33.33%) corresponded to B.1.617.2, a VOC.
Introduction: In five cases (41.67%), the E484K mutation was wrongly assigned by RT-PCR, corresponding to E484Q (B.1 and B.1.280 variants; Table 1).
Introduction: It harbors several mutations affecting the spike protein, including E484K and N501Y.
Introduction: Of these candidates, 121 (85.21%) harbored the E484K and N501Y mutations (B.1.351/P1 candidates as per commercial kit indications), 12 (8.45%) harbored the E484K mutation (B.1.525 candidates), and none
Genomic surveillance of SARS-CoV-2 tracks early interstate transmission of P.1 lineage and diversification within P.2 clade in Brazil.
Abstract: We also identified the occurrence of a new lineage descending from B.1.1.33 that convergently carries the E484K mutation, N.9.
Result: Finally, we report the occurrence of a single sample from the state of Rio Grande do Norte classified as B.1.1.29 that contains both E484K and N429K, uncharacteristic mutations in the lineage.
Result: To confirm its monophyly, we have reconstructed this clade's phylogeny while further increasing the sampling of N.9 sequences to contain all genomes with the E484K available at GISAID (Fig 1).
Result: We found 16 SNVs targeting the receptor-binding domain (RBD) in S1, of which eight were missense variants, including K417T, N439K, L452R,
Ten emerging SARS-CoV-2 spike variants exhibit variable infectivity, animal tropism, and antibody neutralization.
Introduction: Additionally, a new variant B.1.1.318 recently appeared in the United Kingdom; this variant requires close attention because of its E484K mutation.
Introduction: B.1.351(beta or 501Y.V2) first appeared in South Africa and leads to immune escape of the spike protein because of mutation E484K in the RBD; this variant may influence the efficacies of vaccines and therapeutic monoclonal antibodies (mAbs) and sera.
Result: B.1.1.7 variant-infected sera also showed the highest neutralization activity against the variant itself; it was comparatively resistant to B.1.351 and other E484K-carrying sera.
Result: However, an obvious decrease in neutralization sensitivity of E484K-containing SARS-CoV-2 variants was apparent in the vaccine group, especially the inact
Structure-Function Analysis of Resistance to Bamlanivimab by SARS-CoV-2 Variants Kappa, Delta, and Lambda.
PMID: 34648284
2021
Journal of chemical information and modeling
Introduction: Also, the E484Q mutation is similar to E484K found in the Beta and Gamma variants.
Introduction: Similarly, the N501Y mutation found in the B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.1.28.1 (Gamma) variants has been demonstrated to increase the binding affinity between the receptor-binding domain (RBD) and its human receptor ACE2 (hACE2), making these variants more transmissible.- Moreover, experimental and computational studies have showed that Discussion: Our alchemy FEP calculations show that binding free energy changes for L452R and E484K mutations are 3.04 and 22.22 kcal/mol, respectively, indicating that these two mutations substantially weaken the binding between RBD-v and LY-CoV555 and thus are evasive.
In vivo characterization of emerging SARS-CoV-2 variant infectivity and human antibody escape potential.
Discussion: As the pandemic continues, SARS-CoV-2 variants with greater immune escape potential, such as those modeled using the N501Y + K417N + E484K + D614G variant PsV, have dominated new COVID-19 cases globally.
Discussion: In future murine PsV reinfection studies, the N501Y + K417N + E484K + D614G PsV could be used for primary infection, followed by other emerging variant PsVs.
Discussion: It was interesting that there was no significant difference in IgAs' and IgMs' ability to bind the WT versus N501Y + K417N + E484K + D61
Genomic reconstruction of the SARS-CoV-2 epidemic in England.
Abstract: Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions.
Introduction: A phylogeographical analysis establishing the most parsimonious sets of monophyletic and exclusively domestic clades, which can be interpreted as individual introductions, confirmed that A.23.1 with E484K (1 clade) probably has a domestic origin as no genomes of the same clade were observed internationally (Methods.
Introduction: In contrast to other VOCs, Delta/Kappa do not contain N501Y or E484K mutations, but their L452R mutation may reduce antibody recognition and P681R enhances furin cleavage, similar to the P681H mutation of