Discussion: Analysis of RBD-variant/ACE2 binding affinity revealed that N501Y and E484K exhibited essentially WT affinity for ACE2, where WT corresponds to the Wuhan-1 SARS-CoV-2 RBD sequence.
Discussion: Combined, the 3 SARS-CoV-2 RBD variants (K417T, E484K, and N501Y) present in the P.1 Japan/Brazil and B.1.351 South Africa VoC significantly disrupted the binding of 65% of the NAbs tested.
Discussion: Like N501Y and E484K, K417T also significantly disrupts NAb binding.
Discussion: Overall, our data suggests that N501Y and PMID: 34159336
2021
bioRxiv
Result: N501Y has also been shown to reduce susceptibility to some nAbs, although the B.1.1.7 variant appears to remain susceptible to some extent to natural infection-acquired and vaccine-induced nAbs.
Result: Of the five remaining VRVs in the W1 haplotype, A570, T716, and S982 seem relatively benign in that mutations at these positions are already decreasing in certain states/territories (this trend is also true to some extent for N501Y).
Result: The N501Y mutation (present in the B.1.1.7 variant) is located in the receptor-binding domain (RBD) and has been reported to enhance binding affinity to the angiotensin-converting enzyme-2.
Preliminary Structural Data Revealed That the SARS-CoV-2 B.1.617 Variant's RBD Binds to ACE2 Receptor Stronger Than the Wild Type to Enhance the Infectivity.
Introduction: More worrisome is the continuous spread of new SARS-CoV-2 strains in South Africa (B.1.351) and the United Kingdom (B.1.1.7), carrying mutations of N501Y and E484 K within the RBD domain.
Introduction: These mutations in this strain may enhance virus transmissibility and infectivity, including the deletion of residues 69-70 and 144 and the substitution of A570D, D614G, T716I, S982A, D1118H, P681H, K417N, K417T, E484 K and N501Y.
Allosteric Cross-Talk among Spike's Receptor-Binding Domain Mutations of the SARS-CoV-2 South African Variant Triggers an Effective Hijacking of Human Cell Receptor.
PMID: 34161095
2021
The journal of physical chemistry letters
Introduction: Although the total binding free energies (DeltaGb) of the distinct RBD/ACE2 adducts, calculated with the molecular mechanics/generalized born surface area (MM-GBSA) method, do not enable one to discriminate the subtle differences between WT and mutant RBD/ACE2 adducts (Table S3), a dissection of the per-residue amino acids DeltaGb contributions showed an increase, related to the N501Y substitution, with respect to the WT by 3.8 +- 2.0 and 4.4 +- 2.0 kcal/mol in SARBD/ACE2 and N501YRBD/ACE2, respectively (Figure S4), in agreement with recently reported theoretical and experimental evidence.
Introduction: As a result, we disclose that while N501Y (hallmark of the UK variant) enhances the binding affinity toward ACE2 and increases the alpha1-helix@ACE2 bending, the SA strain exploits a two-pronged strategy
Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7.
Method: The mutations (Delta69/70, Delta144, N501Y, A570D,
Figure: (A) Maximum-likelihood phylogeny of global SARS-CoV-2 whole-genome sequences, highlighting those with specific mutations in spike: DeltaH69/V70, N439K, Y453F, and N501Y.
Figure: (B and C) Cumulative occurrences of SARS-CoV-2 sequences with DeltaH69/V70 by month for (B) DeltaH69/V70 with or without N439K/Y453F and (C) DeltaH69/V70 with N501Y.
Figure: Grey bars on the right show the presence or absence of the DeltaH69/V70 and amino acid variants N439K, Y453F, and N501Y.
Analysis of SARS-CoV-2 variant mutations reveals neutralization escape mechanisms and the ability to use ACE2 receptors from additional species.
Result: As shown in Figure 4 , the three variants B.1.1.7, B.1.351, and P.1 gained substantial ability to infect HeLa mouse ACE2, which correlated with pseudoviruses bearing single (K417N, K417T, E484K, and N501Y) and triple (K417N-E484K-N501Y) mutations.
Result: Last, soluble human ACE2 showed improved binding to all three variants as well as pseudoviruses bearing single N501Y and triple K417N-E484K-N501Y mutations (Figure 1D; Figure S2).
Result: Single N501Y mutations found in B.1.1.7 and two of three (K417N and PMID: 34170525
2021
Journal of medical virology
Abstract: Genotyping by RT-ddPCR offers an alternative to rapidly detect VOCs through discrimination of specific alleles such as N501Y, which is associated with increased transmissibility and virulence.
Abstract: Real-time epidemiological tracking of variants of concern (VOCs) can help limit the spread of more contagious forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), such as those containing the N501Y mutation.
Abstract: S gene target failures (SGTF) were subsequently assayed by RT-ddPCR to confirm four mutations within the S gene associated with the B.1.1.7 lineage: a deletion at amino acid (AA) 69-70 (ACATGT), deletion at AA 145, (TTA), N501Y mutation (TAT), and S982A mutation (GCA).
Discussion: One of the mutations thought to be respo
SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity.
Figure: Chromatograms of nucleotide positions 22,913-22,924 (left) and 23,060-23,068 (right) of parental SARS-CoV-2 (strain WK-521; GISAID ID: EPI_ISL_408667) and the L452R (T22917G in nucleotide), Y453F (A22920T in nucleotide), and N501Y (A23063T in nucleotide) mutants are shown.
Figure: Parental SARS-CoV-2 and the L452R, Y453F, and N501Y mutants (100 plaque-forming units [PFU]) were inoculated into HEK293-ACE2 cells (I and J), A549-ACE2 cells (K), and VeroE6/TMPRSS2 cells (L), and the copy number of viral RNA in the culture supernatant was quantified by real-time PCR.
Figure: The HIV-1-based reporter vir
Landscape-Based Mutational Sensitivity Cartography and Network Community Analysis of the SARS-CoV-2 Spike Protein Structures: Quantifying Functional Effects of the Circulating D614G Variant.
Introduction: Other studies examined dynamics and energetics of the S-D614 and S-G614 proteins in the closed and partially open conformations, suggesting that the S-G614 mutant can improve the interprotomer interactions between S1 and S2 regions.- MD simulations of other circulating variants revealed that the N501Y mutation increases ACE2-binding affinity.
Evaluation of a fully automated high-throughput SARS-CoV-2 multiplex qPCR assay with built-in screening functionality for del-HV69/70- and N501Y variants such as B.1.1.7.
Introduction: 3 of the 85 non-B.1.1.7 samples (B.1.258 lineage) were positive for del-HV69/70, but not N501Y, which was confirmed by the TIB MOL reference assays (Table 3 ).
Introduction: 50 B1.1.7 lineage samples were classified as positive for N501Y and del-HV69/70.
Introduction: Additionally, all samples were tested with a set of commercial assays to confirm the relevant mutations (TIB MOL, VirSNiP Spike N501Y and Del69/70, Berlin, Germany).
Introduction: An additional assay was designed (using Beacon designer and PrimerQuest software) and integrated into the multiplex to detect the N501Y SNP.
Introduction: In particular, non-synonymous spike-gene mutations such as the N501Y SNP (single nucleotide polymorphism) may
SARS_CoV_2 mutation literature information.
PMID: 
2021
Frontiers in immunology
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