Abstract: We describe the enhanced affinity of RBD variants N439K, S477N, Q493L, S494P, and N501Y to the ACE2 receptor and demonstrate the ability of this assay to bridge a major gap for SARS-CoV-2 research, informing selection of complementary monoclonal antibody candidates and the rapid identification of immune escape to emerging RBD variants following vaccination or natural infection.
Result: Based on the relative EC50 values observed in our multiplex assay, we selected these high -affinity variants, and the emerging N439K variant present in currently circulating lineage B.1.258, as well as E484K, which is a mutation shared by B.1.351, B.1.525, and P.1 lineages, to be prof
Revealing the Threat of Emerging SARS-CoV-2 Mutations to Antibody Therapies.
Abstract: We unveil, for the first time, that high-frequency mutations R346K/S, N439K, G446V, L455F, V483F/A, F486L, F490L/S, Q493L, and S494P might compromise some of mAbs in clinical trials.
Evolutionary Tracking of SARS-CoV-2 Genetic Variants Highlights an Intricate Balance of Stabilizing and Destabilizing Mutations.
Discussion: The antigenic effect of key RBD mutations against the REGN-COV2 cocktail (REGN10933 and REGN10987) showed N439K and K444R variants escaped neutralization only by REGN10987, while E406W escaped both individual REGN-COV2 antibodies and the cocktail.
Ongoing global and regional adaptive evolution of SARS-CoV-2.
Result: Additionally, S N439K, a signature mutation for variant B.1.258_DELTA that has been demonstrated to enable immune escape, is observed in a large portion of the tree.
Mutational analysis in international isolates and drug repurposing against SARS-CoV-2 spike protein: molecular docking and simulation approach.
Binding affinity and mechanisms of SARS-CoV-2 variants.
PMID: 34336146
2021
Computational and structural biotechnology journal
Conclusion: According to the calculations of the binding free energies, the binding affinities of 501Y.V1, N439K, and 501Y.V2 variants were significantly increased by 36.8%, 29.5%, and 19.6%, respectively.
Conclusion: For example, both the 501Y.V1 and N439K variants were able to form new hydrogen bonds, thus enhancing their binding affinity with hACE2.
Conclusion: In conclusion, we investigated the binding affinity and mechanisms of the three most widespread SARS-CoV-2 variants (501Y.V1, 501Y.V2, N439K) based on molecular dynamics simulations and sequence analysis.
Table: N439K
Figure: (a) Schematic domains of the wild-type SARS-CoV-2 spike monomer and the three variants (501Y.V1, 501Y.V2 and N439K), with the N501Y mutatio
Signatures in SARS-CoV-2 spike protein conferring escape to neutralizing antibodies.
Introduction: L452R and N439K are associated with a modest reduction in antibody-dependent neutralization by immune sera, whilst variants containing E484K display a reduction that is moderate to substantial.
Result: However, we observed a reduction in neutralization in some sera against N439K mutant (0.53+-0.45) as reported in, which was not observed when Delta69-70 was added (Figs 2H and S5), and also against L452R mutant (0.48+-0.23) that is associated with the most recent variants of concern B.1.427/9, as reported in.
Neutralizing Activity of Sera from Sputnik V-Vaccinated People against Variants of Concern (VOC: B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3) and Moscow Endemic SARS-CoV-2 Variants.
Result: The RBD variability data obtained for SARS-CoV-2 variants from Moscow patients (Figure 2, dashed lines) are generally consistent with the variability data for Russian sequences available in GISAID (Figure 2, solid lines and Figure S1) showing increasing prevalence of S477N, A522S, E484K, N501Y, T385I, S494P, N439K, K417N, T487K, N501T, and Y508H mutations.
Discussion: A significant percentage of the substitution variants that are becoming common is recorded: S477N + A522S (27.8%), PMID: 34372500
2021
Viruses
Discussion: A decrease in the prevalence of the N439K variant was the exception.
Discussion: In comparison, N439K increases the binding affinity to ACE2 and may be responsible for the immune escape from the convalescent sera and monoclonal antibodies.
Discussion: In this period, we report an expansion of more virulent variants such as B.1.1.7 VOC and strains not associated with the increased transmissibility per se but containing the described above DeltaH69_V70, N439K, or P681H mutations.
Discussion: Interestingly, two genetically convergent strains (Clade 2 and 3) classified as B.1.258 and B.1.221 were responsible for almost 1/3 (29.2%) of the remaining infections in the analyzed period, with Clade 2 characterized by the conjunction of two spike mutations, DeltaH69_V70 and PMID: 34379353
2021
Biotechnology journal
Discussion: It has been demonstrated that N439K mutation which has been found in more than 30 countries confer resistance against several neutralizing monoclonal antibodies, including one authorized for emergency use by the FDA.
SARS_CoV_2 mutation literature information.
PMID: 
2021
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