Result: Specifically, N501Y and Y453F combined with N439K increased affinity for human ACE2 by 5-fold (Figure 4, Suppl.
Result: Using biolayer interferometry (BLI), we measured rates of association and dissociation of the N501Y RBD mutant (B.1.1.7 carries that mutation as its sole RBD mutation), Y453F as found in mink isolates, N439K which is found in some European clades, a combination of Y453F and N439K, E484K (part of B.1.351 and P.1) as well as for the B.1.351 RBDs for a recombinant version of human ACE2.
Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines.
Introduction: The N501Y substitution present in the B.1.1.7 and B.1.351 lineages, the mink-associated Y453F substitution, and the prevalent N439K mutation did not affect the neutralization potency of any RBD-NP- or HexaPro-elicited sera significantly, while these substitutions have been associated with loss of neutralization for some mAbs.
Introduction: To assess the neutralization breadth of RBD-NP-elicited Abs, we evaluated serum neutralizing activity against a panel of pseudotyped viruses comprising wild-type (D614G) SARS-CoV-2 S and nine single-residue SARS-CoV-2 RBD mutants detected in clinical isolates (G446S, Y453F,
In vitro Characterization of Fitness and Convalescent Antibody Neutralization of SARS-CoV-2 Cluster 5 Variant Emerging in Mink at Danish Farms.
Abstract: Potential alterations in antigenicity conferred by amino acid changes in the spike protein that include three substitutions (Y453F, I692V, and M1229I) and a loss of two amino acid residues 69 and 70 (DeltaH69/V70), were evaluated in a virus microneutralization assay.
Result: A two-amino acid residue deletion (DeltaH69/V70) in the N-terminal domain appeared together with the Y453F in August 2020 and occurred in the subsequent Clusters 2, 3, and 4 (Figure 1).
Result: Of these, three amino acid substitutions (Y453F, I692V, and M1229I) and a two amino acid deletion (DeltaH69/V70) occur in the spike protein (Figure 1C and Supplem
Neutralising antibody escape of SARS-CoV-2 spike protein: Risk assessment for antibody-based Covid-19 therapeutics and vaccines.
Abstract: The Spike protein has different hotspots of mutation and deletion, the most dangerous for immune escape being the ones within the receptor binding domain (RBD), such as K417N/T, N439K, L452R, Y453F, S477N, E484K, and N501Y.
The SARS-CoV-2 Y453F mink variant displays a pronounced increase in ACE-2 affinity but does not challenge antibody neutralization.
PMID: 33716040
2021
The Journal of biological chemistry
Discussion: However, a thorough functional characterization of the impact of the Y453F RBD variant on immunity and ACE-2 interaction has so far not been conducted.
Discussion: Recently, three new genetic mutations inducing residue changes in the RBD have been reported in Europe, that is, N439K, Y453F, and N501Y.
Discussion: The Y453F was first identified in Denmark in the summer of 2020 among farmed minks.
Discussion: To further examine the possible inhibition differences between the two RBD variants, we used a traditional vaccine approach applying mice immunized with WT RBD or the full WT ectodomain spike and assess
Result: Interestingly, 4,209 of sequences in lineage ii/B.1.258 also carry the S 69-70 deletion that has occurred independently multiple times in the pandemic and most notably with the Y453F amino acid replacement associated with mink infections.
Discussion: The Y453F mutation has become noteworthy recently for its association with virus circulating in mink farms and its transmission back to humans and the DMS measurement indicating it confers significantly increased hACE2 binding.
Discussion: To date, we know of only one example of published immune escape documented for Y453F, but more examples may arise as this new mutation is investigated further.
Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity.
Introduction: There have also been reports of SARS-CoV-2 transmission between humans and minks in Denmark with a variant called mink cluster 5 or B.1.1.298, which harbors a 2-amino acid deletion and 4 missense mutations including Y453F in RBD.
Result: Separately, the B.1.1.298 variant found in Danish minks contained a Y453F mutation in RBD, and the California variant B.1.429 contained an L452R.
Result: When assessing variants containing one RBD mutation as part of their mutational landscape, the UK variant B.1.1.7 (N501Y), Danish mink variant B.1.1.298 (Y453F), and California variant B.1.429 (L452R) exhibited neutralization that was similar to that of wild-type and
Decreased neutralization of SARS-CoV-2 global variants by therapeutic anti-spike protein monoclonal antibodies.
Abstract: The failure of REGN10933 to neutralize B.1.351 is caused by the K417N and E484K mutations in the receptor binding domain; the failure to neutralize the mink cluster 5 spike protein is caused by the Y453F mutation.
Genomic mutations and changes in protein secondary structure and solvent accessibility of SARS-CoV-2 (COVID-19 virus).
Conclusion: Alternatively, the mutation Y453F occurs in 5 sequences all in Netherlands but the first collected date was on 2020-04-25 and the latest collected date was on 2020-04-29.
Conclusion: These dates are too close, indicating that all the reported Y453F cases may have been infected from another case, whose genome had not been sequenced and reported to the NCBI GenBank.
Table: Y453F
Biological and Clinical Consequences of Integrin Binding via a Rogue RGD Motif in the SARS CoV-2 Spike Protein.
Discussion: Further support for this hypothesis comes from the observation that the double deletion mutant Delta69-Delta70 often co-occurs with the replacements N501Y, N439K and Y453F.
SARS_CoV_2 mutation literature information.
PMID: 
2021
medRxiv
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