In silico analysis of mutant epitopes in new SARS-CoV-2 lineages suggest global enhanced CD8+ T cell reactivity and also signs of immune response escape.
PMID: 35149224
2022
Infection, genetics and evolution
Result: We observed that the nsSNVs P80R, A701V, K417N, K417T, L18F, and R246I had greater antigenicity scores in regard to the REF sequence.
Table: K417T
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.
Emergence in southern France of a new SARS-CoV-2 variant harbouring both N501Y and E484K substitutions in the spike protein.
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).
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.
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.
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.
Potential inhibitor for blocking binding between ACE2 and SARS-CoV-2 spike protein with mutations.
Result: After treatment of the cells with the indicated concentration of GB-1, the number of 293 T cells with high binding to the RBD with K417T-E484K-N501Y mutation was decreased in both ACE2-positive cells and the top population in the 200-300 mug/mL GB-1 treatment group .
Result: Effect of GB-1 on the binding between ACE2 and RBD with K417T-E484K-N501Y mutation.
Result: Next, we investigated the effect of GB-1 on the binding between ACE2 and RBD with K417T-E484K-N501Y mutation through dual-color flow cytometric analysis.
Result: The number of 293 T cells with low binding to the
Molecular Dynamics and MM-PBSA Analysis of the SARS-CoV-2 Gamma Variant in Complex with the hACE-2 Receptor.
Abstract: Our results indicate that mutations E484K and K417T compensate each other in terms of binding affinity, while the mutation N501Y promotes a more convoluted effect.
Abstract: This variant contains the N501Y, E484K and K417T mutations in the receptor binding domain (
Introduction: The gamma variant carries the K417T, E484K and N501Y mutations previously described in RBM.
Introduction: While the K417T mutation results in the loss of a salt bridge with D30, mutation E484K increases the electrostatic complementarity of the binding partners.
SARS-CoV-2 Mutations and Their Impact on Diagnostics, Therapeutics and Vaccines.
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
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.
SARS_CoV_2 mutation literature information.
PMID: 
2022
Infection, genetics and evolution
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