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
Result: At the same time, structural maps for the S-B.1.351 conformations (Figure 6E,F) highlighted the role of the NTD sites (L18F, D80A, D215G) and especially RBD sites (K417N, E484K, N501Y) that belong to the moving regions in slow motions.
Result: Moderate free-energy changes are also seen for K417N and E484K sites in the closed and open states.
Result: Notably, the degree of solvent exposure for the mutated RBD sites K417N, E484K, and N501Y appreciably increased in the S-B.1.351 states, p
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.
Conclusion: In January 2021, Moderna developed a modified vaccine, a boosting dose of mRNA-1273.351, targeting the beta variant and three mutations (E484K, N501Y, and K417N).
Introduction: Convalescence sera obtained from different countries and periods have consistently demonstrated that E484K or triple mutation (K417N/E484K/N501Y) decreased neutralization in pseudo-viral assays.
Introduction: Gaebler et al and Wang et al obtained convalescent plasma at 1.3 months after infection, and the neutralization against the K417N/E484K/N501Y mutant was reduced 0.5- to 29-fold (P = 0.0
Table: K417N
Structural and biochemical rationale for enhanced spike protein fitness in delta and kappa SARS-CoV-2 variants.
Result: Precedence for compensatory mutations towards increasing ACE2 affinity while decreasing antibody binding has been reported for the N501Y and K417N/T mutational combinations found in the Beta and Gamma variants.
Discussion: Consistent with previous mutational studies that used S proteins with the K417N mutation alone, recent results have demonstrated enhanced immune evasion and decreased ACE2 affinity for the Delta plus (B.1.617.2+) variant relative to Delta (B.1.617.2).
Discussion: The consistency of the effects imparted by the K417N substitution, in isolation or when combined with other mutations, consolidates the understanding of naturally selected mutations as mostly independent functional modules at the molecular level.
Discussion: The deleterious effect of decreased ACE2 affinity imp
Result: First, the 10 most observed or fast-growing RBD mutations are N501Y, L452R, T478K, E484K, K417T, S477N, N439K, K417N, F490S, and S494P, as shown in Ta
Figure: Y449S and K417N are highly disruptive to antibodies.
Figure: Notably, there are two blues lines in the panel of FR due to the same frequency of [K417N, E484K, N501Y] and [E484K, N501Y].
mRNA-1273 Vaccine-elicited Neutralization of SARS-CoV-2 Omicron in Adolescents and Children.
Method: In each variant, the Alpha includes N501Y mutation, Delta has L452R and T478K mutations, and Omicron contains 15 mutated amino acids, i.e., G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q483K/R, G496S, Q498R, N501Y, and Y505H (see also Figures 1B and 2D).
Omicron variant (B.1.1.529) of SARS-CoV-2: understanding mutations in the genome, S-glycoprotein, and antibody-binding regions.
Abstract: Furthermore, we examined the effect of significant antibody-binding mutations (K417N, T478K, E484A, and N501Y) on antibody affinity, stability to ACE2 interaction, and possibility of amino acid substitution.
Abstract: There are several mutations in the antibody-binding region including K417N, E484A, Q493K, Q498R, N501Y, and Y505H and several near the antibody-binding region (S477N, T478K, G496S, G446S, and N440K).
Figure: In the figure, red arrows
Divergent SARS-CoV-2 Omicron-reactive T and B cell responses in COVID-19 vaccine recipients.