Allosteric Determinants of the SARS-CoV-2 Spike Protein Binding with Nanobodies: Examining Mechanisms of Mutational Escape and Sensitivity of the Omicron Variant.
PMID: 35216287
2022
International journal of molecular sciences
Introduction: Neutralization of SARS-CoV-2 by low-picomolar and mutation-tolerant VHH nanobodies that bind synergistically to the opposite sides of the RBD produced a binding avidity effect unaffected by immune-escape mutants K417N/T, E484K, N501Y, and L452R.
Introduction: The detection of common mutational changes such as D614G, E484K, N501Y, and K417N that are shared among major circulating variants B.1.1.7, B.1.351, and B.1.1.28/P.1 indicated that these positions could be particularly critical for modulation of the SARS-CoV-2 S protein responses.
Introduction: These studies identified a group of common resistant mutations in
SARS-CoV-2 Omicron Spike recognition by plasma from individuals receiving BNT162b2 mRNA vaccination with a 16-week interval between doses.
Introduction: The accumulation of E484K and K417N/T mutations along with N501Y in the receptor binding domain (RBD) led to the emergence of Beta (B.1.351) and Gamma (P.1) lineages, which rapidly spread worldwide.
Discussion: Previous in vitro studies already showed the association of some of these mutations with increased infectivity, ACE2 interaction (N501Y, P681H), or immune evasion (K417N, N440K, G446S, S477N, E484A/K, Q493R).
A Detailed Overview of Immune Escape, Antibody Escape, Partial Vaccine Escape of SARS-CoV-2 and Their Emerging Variants With Escape Mutations.
Introduction: Among these four mutations, the E484K mutation is a very significant mutation among these mutations.
Introduction: At the same time, the E484K mutation is accountable for class 2 antibody escape.
Introduction: Few mutations include K417T/N, E484K, L452R, N501Y, <
Introduction: developed pseudoviruses with different RBD mutations or other parts of S-glycoprotein such as N501Y, K417N/T, and E484K, to illustrate the neutralization event.
Table: E484K
Molecular and Epidemiological Characterization of Emerging Immune-Escape Variants of SARS-CoV-2.
Abstract: We found that the Mu variant and a derivative of the Delta strain with E484K and N501Y mutations significantly evaded vaccine-elicited neutralizing antibodies.
Result: Delta + E484K + N501Y
Result: Delta + E484K + N501Y and Mu showed a pattern similar to that of Beta, with 73.8% and 78.6% of the samples strongly neutralized, respectively.
Discussion: In particular, only about 15-30% of vaccinees showed potent neutralizing activity against Delta, Delta + E484K + N501Y, and Mu strains.
Discussion: These strains commonly include the E484K mutation, and this mutation is considered to be a limitation associated with casirivimab, as previously indicated.
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.
PMID: 35231807
2022
Diagnostic microbiology and infectious disease
Result: Accordingly, while we cannot exclude the possibility that this E484K substrain was pre-existing at a very low level, our intense yet incomplete surveillance did not find any evidence of it.
Result: Firstly, despite widespread regional surveillance, we did not detect this B.1.311/E484K lineage in any patient except those associated with this particular household.
Result: In addition to the E484K described in our Minnesota cluster, we found examples in New York (1 sequenced case) and California (2 cases), and an E484Q case in Maryland.
Result: Lineage analysis using Pangolin assigned it to B.1.311, a lineage in which Spike:E484K had not been previously detected.
Result: No additional genomes on the Minnesota E484K su
SARS-CoV-2 Beta and Delta variants trigger Fc effector function with increased cross-reactivity.
Method: For ELISA, ADCP and ADCD assays, SARS-CoV-2 original and Beta variant full spike (L18F, D80A, D215G, K417N, E484K, N501Y, D614G, A701V, 242-244 del), RBD original and Beta (K417N, E484K and N501Y, D614G) and NTD original and Beta (L18F, D80A, D215G and 242-244 del) proteins were expressed in Human Embryonic Kidney (HEK) 293F suspension cells by transfecting the cells with the respective expression pl
Age-Specific Changes in Virulence Associated with SARS-CoV-2 Variants of Concern.
Method: Initial screening focused on the N501Y mutation, with screening for both N501Y and E484K initiated in March 2020.
Method: We used Ontario's Case and Contact Management (CCM) database to create a retrospective cohort of SARS-CoV-2 cases who underwent screening for VOCs and had test report dates between 7 February 2021 and 31 October 2021 (as routine screening for N501Y and E484K mutations began on 7 February 2021).
Human serum from SARS-CoV-2-vaccinated and COVID-19 patients shows reduced binding to the RBD of SARS-CoV-2 Omicron variant.
Introduction: Moreover, a B.1.1.7 sub-lineage with an additional E484K substitution in the RBD has been detected in multiple countries.
Introduction: The E484K amino acid change is also found in other VOCs/VOIs and has been shown to reduce antibody neutralization.
Discussion: Interestingly, the VOCs B.1.351 and P.1 escaped LY-COV555 and REGN10933 which was likely facilitated by the E484K mutation present in both variants.
Discussion: This suggests that L452R and E484K lead to an escape from LY-COV555 and to a partial resistance to either REGN10987 or REGN10933, respectively.
Impact of temperature on the affinity of SARS-CoV-2 Spike glycoprotein for host ACE2.
PMID: 34478710
2021
The Journal of biological chemistry
Result: S1), notably mutations L452R (8.8%), E484K (7.7%), T478K (5.9%), S477N (2.2%), and N439K (1.2%), which are also found in other various VOCs and were shown to either increase infectivity or promote the evasion of antibody responses.
SARS_CoV_2 mutation literature information.
PMID: 
2022
International journal of molecular sciences
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