Method: P2 stock was sequenced and confirmed Omicron with the following substitutions: E:T9I,M:D3G,M:Q19E,M:A63T,N:P13L,N:R203K,N:G204R,ORF1a:K856R,ORF1a:L2084I,ORF1a:A2710T,ORF1a:T3255I,ORF1a:P3395H, PMID: 34931193
2021
bioRxiv
Result: G339D may permit the formation of a novel sidechain interaction while N440K may allow an additional hydrogen bond with its backbone.
Result: However, the (low consensus) prediction of a stabilizing effect of N440K appears to be in contradiction with some previous experimental results.
Result: In our structural analysis, G339D and N440K were indicated to be energetically-favorable substitutions in two out of four omRBD-S309 models each.
Result: Previous studies of S309, VIR-7831, or VIR-7832 have indicated that G339D and N440K have negligible effects on antibody-binding reduction, ranging from 0.5-1.2-fold reduct
Result: found an escape fraction of 0.551 for REGN10987 with N440K.
Importation, circulation, and emergence of variants of SARS-CoV-2 in the South Indian state of Karnataka.
Discussion: The immune escape associated amino acid change, N440K has been reported from the states of Andhra Pradesh, Maharashtra, Telangana, and Karnataka, and is also associated with reinfection, .
Discussion: The lineage is characterized by the following amino acid replacements- nsp12-P323L(95.38%), S-D614G (93.85%), S-N440K (56.92%), ORF 3a-Q57H (90.77%), ORF 3a-E261*(81.54%), nsp3-T183I (81.54%), nsp16-L126F(80%),
Discussion: They occurred singly or in pairs (N440K+F490S) ( Figure 2).
Booster of mRNA-1273 Strengthens SARS-CoV-2 Omicron Neutralization.
Result: All the missed mutations were due to a lack of coverage (<10 reads) and were grouped on the same amplicon NC_045512.2:22903-23122 (missing mutations: N440K, S477N, T478K, E484K, N501Y, A522S).
SARS-CoV-2 Omicron neutralization by therapeutic antibodies, convalescent sera, and post-mRNA vaccine booster.
Introduction: The predominant strain of Omicron has mutations in the spike gene encoding 15 amino acid changes in the receptor binding domain (RBD) of the spike surface protein (G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, and Y505H).
Omicron: A Heavily Mutated SARS-CoV-2 Variant Exhibits Stronger Binding to ACE2 and Potently Escapes Approved COVID-19 Therapeutic Antibodies.
Result: In addition, energy perturbation per amino acid could confirm that the four amino acids, i.e., N440K, T478K, Q493K, and Q498R, directly contribute to the change of the total energy and the electrostatic potential, whereas K417N and E484A compensate the energy change ( Figure 2C ).
Result: We also investigated the change in electrostatic potential of
Discussion: N440K and K444Q can escape against REGN10987, while K417N, N460T, and A475V can successfully escape against LY-CoV016 antibody (AbCellera), currently approved by the FDA for COVID-19 therapy.
Phylodynamic Pattern of Genetic Clusters, Paradigm Shift on Spatio-Temporal Distribution of Clades, and Impact of Spike Glycoprotein Mutations of SARS-CoV-2 Isolates from India.
PMID: 35017872
2021
Journal of global infectious diseases
Result: Among the mutations in RBD, R346K, N440K, G446V, N450K, V483F, E484K, E484Q, F490S and S494P also showed change in ACE2 binding to the extent of 75% to 90%.
Discussion: In contrast, the report suggested that mutations such as L54F, G431S, E471D, G502R, Q506H, P507S, Y508N, E583D and Q675H could weaken the interaction
The plasmablast response to SARS-CoV-2 mRNA vaccination is dominated by non-neutralizing antibodies and targets both the NTD and the RBD.
Result: For sera from the six vaccinated individuals, however, the highest reduction seen was only two-fold for E406Q, N440K, E484K and F490K (Figure 5B).