Conformational Flexibility and Local Frustration in the Functional States of the SARS-CoV-2 Spike B.1.1.7 and B.1.351 Variants: Mutation-Induced Allosteric Modulation Mechanism of Functional Dynamics and Protein Stability.
PMID: 35163572
2022
International journal of molecular sciences
Introduction: These studies suggested that the N501Y and S477N mutations enhance transmission primarily by enhancing binding, and that the K417N/T mutations facilitate immune escape, and the E484K mutation enhances binding and immune escape.
Introduction: This study showed that N501Y, E484K, and L452R mutations can modulate, either directly or allosterically, the increased ACE2 binding affinity, while E484K, L452R, and K417N/T mutations tend to primarily compromise productive antibody binding and induce immune escape.
Real-Time RT-PCR Allelic Discrimination Assay for Detection of N501Y Mutation in the Spike Protein of SARS-CoV-2 Associated with B.1.1.7 Variant of Concern.
Method: Clinical specimens that met these criteria with a CT value of <=30 underwent Sanger sequencing of a 698-bp (nucleotide positions 22516 to 23214) S gene fragment, which includes the locations of key receptor-binding domain (RBD) mutations (K417N/T, E484K, and N501Y).
Discussion: Other SNP assays have been developed for important S gene SNPs that characterize VOCs, including E484K (P.1, B.1.351), K417N/T (P.1, B.1.351), and L452R (B.1.617.2).
Genomic Surveillance of SARS-CoV-2 Lineages Indicates Early Circulation of P.1 (Gamma) Variant of Concern in Southern Brazil.
Introduction: The P.1 lineage-defining mutations in the Spike protein, especially in the receptor-binding domains (RBD) such as K417T, E484K and N501Y, are of concern because they may enhance ACE2 affinity and contribute to antibody evasion.
Table: K417T
Discussion: According to our results, most of the P.1 sequences carried the 22 lineage-defining mutations, including the three mutations in the Spike protein, RBD domain (K417T, E484K and N501Y) associated with evasion of the immune system and greater transmissibility.
mRNA vaccine-induced antibodies more effective than natural immunity in neutralizing SARS-CoV-2 and its high affinity variants.
Introduction: N501Y and two other mutations in the RBD domain, K417N/T and E484K, were subsequently founds in SARS-CoV-2 variants from South Africa (B.1.351) and Brazil (P.1).
Discussion: Other RBD mutations, K417N/T and E484K, either alone or in combinations, have not been evaluated in this study.
Cross-Neutralizing Breadth and Longevity Against SARS-CoV-2 Variants After Infections.
Introduction: P.1, which was identified in Brazil, has three mutations (K417T, E484K, and N501Y) in the RBD.
Introduction: The K417N mutation of B.1.351 and B.1.1.529 and K417T mutation of P.1 are suggested to change the conformation of S protein, allowing escape from Nabs.
Early Genomic, Epidemiological, and Clinical Description of the SARS-CoV-2 Omicron Variant in Mexico City.
Result: K417N/T is present in the Alpha and Gamma variants, and both mutations facilitate immune escape for monoclonal antibodies (bamlanivimab/LY-CoV555), escape from neutralization by convalescent plasma, and escape by sera from BNT162b2-vaccinated individuals.
Decreased and Heterogeneous Neutralizing Antibody Responses Against RBD of SARS-CoV-2 Variants After mRNA Vaccination.
Method: Primers used for the construction of the RBD-mFc proteins for the different variants (Alpha RBD-mFc, containing mutation N501Y; Gamma RBD-mFc containing mutations K417T, E484K, and N501Y; Delta RBD-mFc containing mutations L452R and T478K); Epsilon RBD-mFc containing mutation L452R; and Kappa RBD-mFc containing mutations L452R and E484Q), were obtained from Sigma-Aldrich and are shown in Supplementary Table 2 .
Neutralisation Hierarchy of SARS-CoV-2 Variants of Concern Using Standardised, Quantitative Neutralisation Assays Reveals a Correlation With Disease Severity; Towards Deciphering Protective Antibody Thresholds.
Introduction: For the P.1 variant carrying K417T + E484K + N501Y, neutralization assays using pseudotyped virus-like particles showed a reduction in neutralization (FDA).
Introduction: Similarly, K417N/T found in B.1.351 and P.1 was also found to evade antibody binding, though less potent than E484 substitutions (https://covariants.org/variants/S.E484).
Table: K417N/T
Table: K417T
A SARS-CoV-2 Wuhan spike virosome vaccine induces superior neutralization breadth compared to one using the Beta spike.
Method: Pre-fusion spike protein ectodomain DNA constructs were designed containing the following mutations compared to the Wuhan variant (Wuhan Hu-1; GenBank: MN908947.3): deletion of H69, V70 and Y144, N501Y, A570D, D614G, P681H, T716I, S982A and D1118H in Alpha; L18F, D80A, D215G, L242H, R246I, K417N, E484K, N501Y, D614G and A701V in Beta;
SARS_CoV_2 mutation literature information.
PMID: 
2022
International journal of molecular sciences
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