Discussion: For example, the Alpha variant that often also has N501Y, N439K, and Y453F mutations appears to require a deletion (DeltaH69/V70) in the spike protein to maintain optimal cleavage and infectivity.
Receptor binding, immune escape, and protein stability direct the natural selection of SARS-CoV-2 variants.
PMID: 34543625
2021
The Journal of biological chemistry
Introduction: These include 9 single site mutations K417N, N439K, Y453F, S477N, S477I, T478I, E484K, S494P and N501Y (Alpha variant), a double mutant (E484K/N501Y) and two triple mutants (K417N/E484K/N501Y (Beta variant) and
Result: Among 9 single site mutants, 2 mutants (N439K and S477I) did not express very well and appreciable amount of protein needed for binding studies could not be obtained for these mutants.
Mutations of SARS-CoV-2 RBD May Alter Its Molecular Structure to Improve Its Infection Efficiency.
Abstract: Interestingly, N501Y, N439K, and E484K mutations were observed to increase the rigidity in some
Method: Afterward, the sequences were uploaded to Iterative Threading Assembly Refinement (I-TASSER) platform to model the starting structures for the L452R, S477N, N439K, and E484K mutants before MD simulations.
Method: The starting coordinates for each MD simulation system were either X-ray structures (i.e., for the WT RBD and N501Y mutants) or the modeled structures for the L452R, S477N, N439K, and E484K mutants.
Genomic epidemiological analysis of SARS-CoV-2 household transmission.
Discussion: These include D614G, associated with the B.1 lineage observed in this family cluster, which is now ubiquitous and appears to have a moderate effect on SARS-CoV-2 transmissibility; A222V, present in the 20A.EU1 (B.1.177) cluster which has spread quickly across Europe from Spain and become dominant in Irish sequences; and N439K, a variant for which there is evidence to suggest increased ACE2 receptor binding affinity and immune-escape from neutralising antibodies.
Rapid and High-Throughput Reverse Transcriptase Quantitative PCR (RT-qPCR) Assay for Identification and Differentiation between SARS-CoV-2 Variants B.1.1.7 and B.1.351.
Result: We found 16 SNVs targeting the receptor-binding domain (RBD) in S1, of which eight were missense variants, including K417T, N439K, L452R, S477R, E484K, N501Y, L518I, A522V.
Discussion: Finally, the third newly-detected convergent event described in this work is the E484K and N439K variants in a sample of B.1.1.29 from Rio Grande do Norte.
Discussion: Indeed, all convergent mutations aforementioned are somehow associated with viral escape from immune system response: N439K has shown to escape immune escape from both polyclonal and monoclonal antibodies; <
Bioinformatics analysis of the differences in the binding profile of the wild-type and mutants of the SARS-CoV-2 spike protein variants with the ACE2 receptor.
PMID: 34655895
2021
Computers in biology and medicine
Result: According to the MM/GBSA analysis, the reported mutations (N439K, S477 N, and
Figure: (a) show the comparative RMSD of the wild type and N439K, (b) show the comparative RMSD of the wild type and S477 N, while (c) show the comparative RMSD of the wild type and T478K.
Figure: (a) show the comparative total number of hydrogen bonds of the wild type and N439K, (b) show the comparative total number of hydrogen bonds of the wild type and S477 N while (c) show the comparative total number of hydrogen bonds of the wild type and T478K.
Figure: (b) The binding interface and stick representation of hydrogen bonding of the N439K mutant complex.
Global Prevalence of Adaptive and Prolonged Infections' Mutations in the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein.
Result: Further, we observed a considerable prevalence of other adaptive mutations in the RBD, namely L452R, T478K, E484K, S477N, K417T, N439K and S494P.
Result: In T3, mutations N439K, Y453F, S477N, V483A, E484K, E484Q, S494P and N501Y were observed.
Result: In the case of the N439K mutation, studies have shown enhanced binding to the ACE2 receptor.
Result: Like the
Temporal-Geographical Dispersion of SARS-CoV-2 Spike Glycoprotein Variant Lineages and Their Functional Prediction Using in Silico Approach.
Abstract: Through in silico protein structure prediction and immunoinformatics tools, we discovered D614G is the key determinant to S protein conformational change, while variations of N439K, T478I, E484K, and N501Y in S1-RBD also had an impact on S protein binding affinity to hACE2 and antigenicity.
Introduction: Besides D614G, amino acid changes within S1-RBD, such as N439K, L452R, E484K/Q, and N501Y, also favor virus resistance to monoclonal antibody neutralization.
Discussion: SARS-
Prediction of the Effects of Variants and Differential Expression of Key Host Genes ACE2, TMPRSS2, and FURIN in SARS-CoV-2 Pathogenesis: An In Silico Approach.
PMID: 34720581
2021
Bioinformatics and biology insights
Result: We also analyzed the effect of 27 missense variants of SARS-CoV-2 spike protein (RBD) on the binding interaction of spike protein with ACE2 and observed that L452Q, T478K, L455F, F456L, S459F, A475V, N439K, L452R, T470N, E484D, E484A, E484K, E484Q, F486L, S494P, S494L, N501T,