Result: For example, a recent study showed that N439K compensated for an RBM mutation K417V that otherwise decreases the receptor-binding affinity and that several mAbs were more sensitive to these mutations in combination versus individually.
The alpha/B.1.1.7 SARS-CoV-2 variant exhibits significantly higher affinity for ACE-2 and requires lower inoculation doses to cause disease in K18-hACE2 mice.
Result: Determination of the evasion capacity of the N439K and N501Y variants in naturally induced antibody-mediated immunity.
Result: However, best-fit IC50 values from sera from mice immunized with spike differed slightly between strains, as 11% and 19% higher serum concentration was required for the N439K and N501Y variants, respectively, to achieve the same inhibition levels as for the wt RBD.
Result: Linear regression and Spearman correlation analyses of the mAbs with best-fit IC50s within the range of concentration tested (n = 8) showed that the N439K and N501Y mutations had very minor effects on the inhibition potency of the mAbs (N439K R2 = 0.9777, rho = 1, p <
Additional Positive Electric Residues in the Crucial Spike Glycoprotein S Regions of the New SARS-CoV-2 Variants.
The Development of SARS-CoV-2 Variants: The Gene Makes the Disease.
PMID: 34940505
2021
Journal of developmental biology
Introduction: N439K has also been shown to enhance the binding affinity for the ACE2 receptor.
Introduction: Its appearance is recurrent and often co-occurs with N439K, Y453F, and N501Y mutations, suggesting a selective advantage and possible epistasis between mutations, which should be further examined.
Introduction: Mutation Y453F, along with N439K, G446V, K444E, and S477N, among others, which are located at the interface between the S1 and ACE2, have been shown to partially interfere with antibody binding and neutralization.
A Conservative Replacement in the Transmembrane Domain of SARS-CoV-2 ORF7a as a Putative Risk Factor in COVID-19.
Abstract: Well-characterized mutations in the spike protein, such as D614G, N439K, Delta69-70, E484K, or N501Y, are currently defining specific variants; however, some less studied mutations outside the spike region, such as p.
Low Represented Mutation Clustering in SARS-CoV-2 B.1.1.7 Sublineage Group with Synonymous Mutations in the E Gene.
Abstract: Interestingly, these samples also harbored three other mutations (S137L-Orf1ab; N439K-S gene; A156S-N gene), which had a very low diffusion rate worldwide.
Introduction: Thus, the samples were sequenced, which revealed the presence of a synonymous mutation (c.26415 C > T, TAC > TAT, Reference Genome: NC_045512) in the E gene and three other mutations (S137L:Orf1ab gene, N439K:Spike gene, and A156S:Nucleocapsid gene) scattered throughout the genome in all samples carrying the PMID: 32699850
2020
bioRxiv
Result: These include N439K in 246 samples (244 Scottish, 1 England, 1 Romania), V483A in 30 samples (26 USA/WA, 2 USA/UN, 1 USA/CT, 1 England), G476S in 18 samples (13 USA/WA, 2 USA/OR, 1 USA/ID, 1 USA/CT, 1 Belgium), S494P in 7 samples (3 USA/MI, 1 England, 1 Spain, 1 India, 1 Sweden), V483I in 2 English samples, and L455I together with F456V in one Brazilian sample.
The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity.
Result: Finally, Y508H reduced the sensitivity to mAb H014, N439K to mAb H00S022, A831V to mAb B38, D614G+I472V to mAb X593, and D614G+A435S to mAb H014 by more than 4 times.
Result: Furthermore, H00S022 was unable to neutralizing N439K and N234Q.
Result: These variants include single amino acid change such as Y145del, Q414E, N439K, G446V, K458N, I472V, A475V, T478I,
Geographic and Genomic Distribution of SARS-CoV-2 Mutations.
Result: The Spike protein, apart from the discussed D614G mutation, has no other event present in more than 1% of the viral population; amongst the top 5, a N439K variant located in the Spike/ACE2 interaction domain is observed in 0.7% of the viruses.
Discussion: The prevalent Spike D614G mutation does not seem to affect the interaction domain with ACE2 (Wang et al.,), responsible for the viral entry into epithelial cells (Guzzi et al.,), but other mutations are currently located in that domain, such as N439K, present in 0.7% of the sequenced SARS-CoV-2 genomes.
A SARS-CoV-2 vaccine candidate would likely match all currently circulating variants.
Discussion: Importantly, we found no mutation in the RBD that was present in more than 1% of SARS-CoV-2 sequences (highest frequency was 0.2% N439K); such rare variants are unlikely to interfere with vaccine efficacy.
SARS_CoV_2 mutation literature information.
PMID: 
2021
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