A Combination of Receptor-Binding Domain and N-Terminal Domain Neutralizing Antibodies Limits the Generation of SARS-CoV-2 Spike Neutralization-Escape Mutants.
Result: In addition to F490S, binding of ADI-56443 was completely abolished by C480S/R, E484K/G/D, C488Y/S, and F490L/I/C RBD mutations.
Result: The E484K mutation is also present in multiple variants including P.1, P.2, B.1.525, and B.1.351, and viruses carrying this mutation are resistant to the currently used MAb therapy.
Evaluation of the relative virulence of novel SARS-CoV-2 variants: a retrospective cohort study in Ontario, Canada.
Introduction: Novel SARS-CoV-2 variants of concern (VOCs), including viral lineages carrying the N501Y (Alpha/B.1.1.7) or both the N501Y and E484K mutations (Beta/B.1.351 and Gamma/P.1), w
Method: 22, 2021, the province initiated universal screening for N501Y and E484K mutations using a multiplex real-time PCR assay on all specimens testing positive for SARS-CoV-2 with a cycle threshold value of 35 or less.
Method: Initially, all specimens with the N501Y or E484K mutation and a cycle threshold value of 30 or less were sequenced; however, as of June 2021, routine whole genome sequencing was no longer performed on specimens without E484K, under the presumption that such specimens were of the Alpha lineage.
Rapid and High-Throughput Reverse Transcriptase Quantitative PCR (RT-qPCR) Assay for Identification and Differentiation between SARS-CoV-2 Variants B.1.1.7 and B.1.351.
Result: Out of 20 suspected samples, four contained the following mutations in the spike gene: D215G, the 242 to 244 deletion, K417N, E484K, and N501Y, all associated with the B.1.351 variant.
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Discussion: A few commercial kits partially address the detection of these SC-2 variants, but they target general mutations, such as N501Y and E484K in the spike protein, and not variant-specific mutations, such as the N protein D3L substitution or the spike protein 242 to 244 deletion (https://www.seegene.com/assays/rp, http://www.kogene.co.kr/eng/sub/product/covid-19.asp).
Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 lineages circulating in Brazil.
Abstract: In summary, we report that ChAdOx1 nCoV-19 protects against emerging variants in Brazil despite the presence of the spike protein mutation E484K.
Introduction: E484K has been associated with in vitro immune escape from therapeutic monoclonal antibodies, prompting the withdrawal of the emergency use authorisation for bamlanivumab in the US.
Introduction: Both the Gamma (P.1) and Zeta (P.2) sublineages harbour the E484K mutation in the receptor binding domain (RBD) of the spike protein.
Introduction: The coincident emergence of N501Y, K417T/N and E484K mutations in Gamma (P.1) and Beta (B.1.351) is suggestive o
Spread of Mink SARS-CoV-2 Variants in Humans: A Model of Sarbecovirus Interspecies Evolution.
Introduction: Based on the 3D modeling of the SARS-CoV-2 spike-human ACE2 interactions we visualized the location of amino acids described as major mutation sites in the SARS-CoV-2 variants infecting humans, i.e., the S477N, E484K, and N501Y/T mutations known to characterize the Marseille-4 variant (France), the 20I/501Y.V1 variant (United Kingdom), and the 20H/501Y.V2 variant (South Africa) (Figure 8A, left panel).
Evaluation of the clinical and analytical performance of the Seegene allplex SARS-CoV-2 variants I assay for the detection of variants of concern (VOC) and variants of interests (VOI).
Introduction: The assay targets the RNA-dependent RNA polymerase (RdRp) gene, the S-protein N501Y and E484K mutations and HV69/70 deletion, as well as an endogenous internal control.
Introduction: Two subsequent variants of concern, B.1.351 (beta variant), first identified in South Africa, and P.1 (gamma variant), first identified in Brazil, were found to harbor the D614G and N501Y mutations, as well as 2 additional key mutations in the receptor binding domain (RBD), K417N/T and E484K, which increase binding affinity to the ACE2 receptor.
A Barcoded Flow Cytometric Assay to Explore the Antibody Responses Against SARS-CoV-2 Spike and Its Variants.
Result: For this, we introduced in the RBD-CD8 construct the N501Y and the E484K point mutations characteristic
Figure: (A) Schematic drawing of the RBD-CD8 protein with either an WT (green), or an N501Y (blue), E484K (red) or G496I (grey) mutated RBD sequence.
Figure: Shown is the IgG (left panel) and IgA (right panel) antibody response of the sera diluted 1:100 and analyzed for binding to Ramos cells expressing RBD-CD8 protein with either a WT (green), or an N501Y (blue), E484K (red) or G496I (grey) mutated RBD sequence.
Cross-Neutralizing Activity Against SARS-CoV-2 Variants in COVID-19 Patients: Comparison of 4 Waves of the Pandemic in Japan.
PMID: 34631915
2021
Open forum infectious diseases
Introduction: Among the 9 mutations in the spike gene in this variant, there are 3 biologically important mutations: K417N, E484K, and N501Y.
Introduction: In addition, the B.1.351 and P.1 variants carry the E484K mutation, which is responsible for evasion from the monoclonal antibody against the original SARS-CoV-2, further compromising the currently available therapy against this virus.
Introduction: It bears 12 mutations in the spike gene, including K417T, E484K, and N501Y, which are the same 3 amino acid substitutions found in B.1.351.
Discussion: However, the E484K mutation, which is found both in P.1 and B.1.351 but not
Mutational profile confers increased stability of SARS-CoV-2 spike protein in Brazilian isolates.
PMID: 34633892
2021
Journal of biomolecular structure & dynamics
Abstract: Mutations E484K, N501Y and K417N belong to several SARS-CoV-2 variants of concern such as Alpha, Beta, Gamma and Delta, and showed high incidence among Brazilian isolates.
SARS-CoV-2 monoclonal antibodies with therapeutic potential: Broad neutralizing activity and No evidence of antibody-dependent enhancement.
Figure: (a) Binding responses of anti-SARS-CoV-2 S protein mAbs, S1D2-hIgG1, STI-1499-LALA and 1741-LALA to the S1 fragment of the S protein from SARS-CoV-2 variants, including 2019-nCoV, B.1.1.7 (HV69-70 deletion, Y144 deletion, N501Y, A570D, D614G, P681H)-, B.1.351 ( Discussion: Further evidence shows receptor-binding domain (RBD) mutations E484K and combined K417N and N501Y mutations of SARS-CoV-2 B.1.351 and P.1 variants as vulnerabilities to multiple SARS-CoV-2 neutralizing mAbs engaging the RBD domain, and polyclonal Abs from convalescent sera or vaccine-induced immune sera.
SARS_CoV_2 mutation literature information.
PMID: 
2021
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