Introduction: Among these mutations, some are linked to the immune system, particularly when present in the RBD, such as E484K and S477N.
Introduction: One branch has the S477N mutation (8.6% of B.1.526 viruses), which is found near the binding site of several antibodies and implicated in the enhancement of Spike-ACE2R interaction.
Introduction: Two cases with S477N have been detected in Auvergne-Rhone-Alpes in France.
Use of Lateral Flow Immunoassay to Characterize SARS-CoV-2 RBD-Specific Antibodies and Their Ability to React with the UK, SA and BR P.1 Variant RBDs.
Introduction: Figure 1 summarizes currently circulating SARS-CoV-2 variants and their respective mutations within the spike RBD, which include the following: N501Y in the UK, SA, and BR-P.1 variants; E484K/Q in the SA, BR P.1, BR P.2, NY, and IN variants; K417N/T in the SA and BR P.1 variants; L452R in the CA and IN variants; S477N in some NY variants; and Y453F in the Denmark mink variant.
The emerging SARS-CoV-2 variants of concern.
PMID: 34211709
2021
Therapeutic advances in infectious disease
Method: E484K has given rise to the B.1.525/B.1.526 lineage seen spreading among New York residents, perhaps because this version is more capable of evading antibodies, as well as binding more tightly to human cells due to the co-S477N mutation.
Discussion: Spike mutation E484K is present in about half of this lineage, with a smaller fraction having S477N instead of E484K.
The Antigenicity of Epidemic SARS-CoV-2 Variants in the United Kingdom.
Abstract: The N501Y, N439K, and S477N mutations caused immune escape from nine of 18 mAbs.
Abstract: To determine whether the neutralization activity of monoclonal antibodies, convalescent sera and vaccine-elicited sera was affected by the top five epidemic SARS-CoV-2 variants in the UK, including D614G+L18F+A222V, D614G+A222V, D614G+S477N, VOC-202012/01(B.1.1.7) and D614G+69-70del+N439K, a pseudovirus-neutralization assay was performed to evaluate the relative neutralization titers against the five SARS-CoV-2 variants and 12 single deconvolution mutants based on the varia
Human immunoglobulin from transchromosomic bovines hyperimmunized with SARS-CoV-2 spike antigen efficiently neutralizes viral variants.
PMID: 34228597
2021
Human vaccines & immunotherapeutics
Abstract: Neutralization potency was retained for S variants including S477N, E484K, and N501Y, substitutions present in recent variants of concern.
Introduction: We demonstrate that SAB-185 retains potent neutralizing activity against the D614G, S477N, E484K, and N501Y&
Discussion: This finding contrasts with earlier work which shows that immune sera obtained from patients that have recovered from COVID-19 as well as several mAbs show significant reductions in neutralization potency in cell culture assays particularly against S substitutions E484K and S477N.
A Novel SARS-CoV-2 Viral Sequence Bioinformatic Pipeline Has Found Genetic Evidence That the Viral 3' Untranslated Region (UTR) Is Evolving and Generating Increased Viral Diversity.
Result: Previously, it has been shown that S477N slightly improves the folding of the Spike protein and the fitness of RBD-ACE2 binding and more flexibility in the NTD could help to bind ACE2 receptor.
Result: Taken together, non-neutral amino acid changes in SARS-CoV-2 can change viral protein motility and might confer improved fitness to the virus, as appears to be the case of the S477N variant.
Result: The A222V change is predicted to decrease the motility of the N-terminal of Spike protein (NTD), while the S477N and V1176F variants are predicted to increase the motility of the Receptor Binding Domain ( PMID: 34245452
2021
Journal of medical virology
Result: It has been reported that G22992A (S:S477N) was in the S protein receptor-binding domain (RBD), which is a flexible and disordered loop in the unbound state but later becomes ordered in all the available ACE2-bound SARS-CoV-2 S structures.
Simultaneous evaluation of antibodies that inhibit SARS-CoV-2 variants via multiplex assay.
Abstract: We describe the enhanced affinity of RBD variants
Result: These were N501Y, Q493L, S494P, and S477N, which demonstrated the lowest overall relative EC50 values (0.2, 3.6, 6.3, and 8.3 mug/mL, respectively) as determined by our ACE2-RBD multiplex assay (Figure 3C).
Result: This included the RBD variant S477N, which emerged and rose to be the second most frequent variant in the following months.
Result: Variant S477N also demonstrated enhanced (KD 10 nM) affinity for ACE2, although variant Q483L (KD 21 nM) demonstrated a slower off rate, t1/2 211.5 seconds versus t1/2 160.6 seconds by comparison.
Evolutionary Tracking of SARS-CoV-2 Genetic Variants Highlights an Intricate Balance of Stabilizing and Destabilizing Mutations.
Result: Amino acid substitutions such as T428I and G15S in ORF1a were reported in sublineages C.1 and C.2, and the S477N substitution in the spike (S) protein along with I120F in nsp2 specifically established the sublineage D.2.
Result: Structural analysis of double (D614G + Table: S477N
Discussion: Our analysis confirmed previously recorded positive natural selection of the D614G, S477N, A222V, and V1176F variants and a global expansion of the PANGOLIN variant B.1.