Mutations in the receptor-binding domain of human SARS CoV-2 spike protein increases its affinity to bind human ACE-2 receptor.
PMID: 35109768
2022
Journal of biomolecular structure & dynamics
Abstract: Here, we use the crystal structure of the RBD in complex with ACE-2 available in the public domain and analyse the 250 ns molecular dynamics (MD) simulations of wild-type and mutants; K417N, K417T, N440K, N501Y, L452R, T478K, E484K and S494P.
Divergent SARS-CoV-2 Omicron-reactive T and B cell responses in COVID-19 vaccine recipients.
Abstract: Further, we engineer a potent ACE2-blocking nAb to sustain binding to S RBD with the E484K and L452R substitutions found in multiple SARS-CoV-2 variants.
Discussion: Further, while we determined it was outside the scope of the current paper, we did not generate/analyze crystal structures of an escape variant such as RBD-E484K in complex with antibodies N-612-017-01/03 in comparison with N-612-017.
Discussion: Our N-612-017 antibody is a class 2 RBD binder similar to bamlanivimab that also displays a loss of activity in the presence of the E484K mutation.
Discussion: To address this potential loss of efficacy, we used affinity maturation for N-612-017 and quickly identified subcl
Breadth of SARS-CoV-2 Neutralization and Protection Induced by a Nanoparticle Vaccine.
Result: Taken together, the missense mutations, Discussion: Higher infectivity of the SARS-CoV-2 variants is associated with increased in binding affinity between spike protein and ACE2 due to K417N, E484K, N439K and N501Y mutations in the RBD of the spike protein.
Discussion: While N501Y mutation alone enhanced spike RBD-ACE2 affinity, combination of K417N, E484K and N501Y mutations in B.1.351 lineage resulted in noticeable conformational changes in RBD when bound to ACE2.
Evolutionary history of the SARS-CoV-2 Gamma variant of concern (P.1): a perfect storm.
PMID: 35266951
2022
Genetics and molecular biology
Introduction: Currently, the WHO has identified the Gamma lineage (B.1.1.28.1, P.1 or Gamma; Nextstrain clade 20J/V3) with the following key S mutations: L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I, and V1176F.
Introduction: The WHO and other reports identified several key SARS-CoV-2
Result: Notably, in our analysis, a number of these sites (e.g., E484K) did not exhibit evidence of positive selection.
Table: E484K
Characterization of SARS-CoV-2 Variants B.1.617.1 (Kappa), B.1.617.2 (Delta), and B.1.618 by Cell Entry and Immune Evasion.
Introduction: Also, the E484Q mutation is similar to the E484K mutation found in the B.1.351 variant, which exhibited reduced neutralization by convalescent-phase sera or monoclonal antibodies.
Introduction: B.1.618 harbors Delta145-146 (deletion of the 145th and 146th residues) and an E484K mutation in the NTD and RBD, respectively.
Introduction: For the Kappa and Delta variants, this is the first time that L452R and E484Q (Kappa)/T478K (Delta) mutations have been found to coexist and the first time that P681R has been observed; for B.1.618, this is the first time the combination of Delta145-146 in the NTD domain and E484K has been observed.
Introduction: In
Insights into the structure and dynamics of SARS-CoV-2 spike glycoprotein double mutant L452R-E484Q.
Introduction: Another variant, B.1.351 (Mwenda et al.) and P.1 variant (Francisco et al.) carries 9 and 11 spike protein mutations, respectively, including 3 mutations in the receptor-binding domain (RBD), K417N/T, E484K, and N501Y.
Vaccine-Induced Antibody Responses against SARS-CoV-2 Variants-Of-Concern Six Months after the BNT162b2 COVID-19 mRNA Vaccination.
Result: including N501Y in both Alpha and Beta, E484K in Eta and Beta, K417N in Beta, and L452R and T478K only in Delta.
Discussion: Amino acid changes in spike proteins of variants contribute to immune evasion, and it has been suggested that N501Y is associated with increased infectivity, whereas L452R, T478K, and E484K with K417N reduce the interaction of neutralizing antibodies with RBD.
Discussion: However, Eta with slightly reduced neutralization results has solely an E484K substitution, indicating that the PMID: 35262087
2022
medRxiv
Abstract: The SNP assays (K417T, E484K, E484Q,
Method: SARS-CoV-2 TaqMan Assays for S substitutions K417T, E484K, E484Q, and L452R were performed per manufacturer's instructions (Thermo Fisher) with 4 muL of template.
Discussion: The accuracies of K417T, E484K, E484Q, and L452R assays were >= 96.4% (Table 3).
Discussion: We did observe low-level amplification from off-target binding in the E484K, K417T, and L452R assays.