Acquisition of the L452R Mutation in the ACE2-Binding Interface of Spike Protein Triggers Recent Massive Expansion of SARS-CoV-2 Variants.
PMID: 34379531
2021
Journal of clinical microbiology
3Introduction: Because of the important functional and antigenic properties of the RBD, structural changes in this domain deserve special attention and have already been highlighted by such notorious RBD mutations as E484K (e.g., found in B.1.1.28, also known as the ""Brazil"" variant or VOI zeta) and N501Y (found in B.1.1.7, also known as the ""British"" variant or VOC alpha, and in B.1.351, also known as the ""South African"" variant or VOC beta)."
Effect of SARS-CoV-2 B.1.1.7 mutations on spike protein structure and function.
Abstract: The N501Y mutation introduces a pi-pi interaction that enhances RBD binding to ACE2 and abolishes binding of a potent neutralizing antibody (nAb).
SARS-CoV-2 receptor-binding mutations and antibody contact sites.
Abstract: We report high frequency mutations with improved binding affinity to ACE2 including S477N, N439K, V367F, and N501Y and address the potential impact of RBD mutations on antibody binding.
Conclusion: In conclusion, we found a number of high frequency SARS-CoV-2 RBD mutations with improved binding affinities to the ACE2 receptor including
Introduction: We found four high frequency variants with improved binding to ACE2:S477N, N439K, V367F, and N501Y and cross-referenced antibody interaction data with RBD mutations.
Table: N501Y
Emergence in southern France of a new SARS-CoV-2 variant harbouring both N501Y and E484K substitutions in the spike protein.
Introduction: Interestingly, we determined that this antigen test loses sensitivity for detecting SARS-CoV-2 variants carrying the K417N/T, E484K and N501Y single nucleotide polymorphisms (SNPs).
Figure: By contrast, in the other 15 positive samples we identified the SARS-CoV-2 variants K417N/T, E484K, and N501Y (gray arrows) (Group 2).
Figure: RAT detection of SARS-CoV-2 variants which contain K417N/T, E484K, and N501Y mutations, from RT-qPCR positive samples with Cq value between 20>=Cq <25, 25>=Cq <30, 30>=Cq <35.
Discussion: Because the amino acid substitutions E484K and N50
RBD Double Mutations of SARS-CoV-2 Strains Increase Transmissibility through Enhanced Interaction between RBD and ACE2 Receptor.
Result: Comparing to the overall free binding energy of 212.5 kJ mol-1 between the wild-type RBD and ACE2 receptor, all single and double RBD mutants showed increased free binding energy, except for N501Y, which decreased to -204.6 kJ mol-1 (Table 1A).
Result: However, N501 became a top residue in two of the three RBD double mutants and four of the five RBD single mutants, highlighting that N501Y in the RBD double mutants and single RBD mutants played significant roles in enhancing the affinity between RBD mutants to the ACE2 receptor by enhancing the binding energy (Table 1B, Figure 4).
Result: However, the top five residues in each PMID: 35062214
2021
Viruses
Result: N501Y has also been shown to reduce susceptibility to some neutralizing antibodies (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 UK-VRV 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.
A Genomic Snapshot of the SARS-CoV-2 Pandemic in the Balearic Islands.
Discussion: This lineage is defined by 14 amino acid changes and three deletions, including six amino acid substitutions and two deletions in the spike protein: S:DeltaH69-V70, S:DeltaY144, S:N501Y, S:A570D, S:P681H, S:T716I, S:S982A, and S:D1118H and it has been related with some evolutionary advantages such as an increased transmissibility.
Molecular Characterization of Severe Acute Respiratory Syndrome Coronavirus 2 Isolates From Central Inner Sardinia.
Result: The III wave was characterized by the appearance of the subset of mutations that distinguish the B.1.1.7 lineage such as H69_V70del, Y144del, N501Y
Discussion: Spike N501Y was associated with a slight but significant reduction in neutralization.
Discussion: All these substitutions were associated with the B.1.1.7 lineage, besides spike N501Y which also characterizes P.1 and B.1.351 lineages, as their corresponding clade nomenclature suggests.
Discussion: Other substitutions were found in specific lineages, such as spike H69_V70del, Y144del, N501Y, or nucleocapsid S235F.
Antidepressant and Antipsychotic Drugs Reduce Viral Infection by SARS-CoV-2 and Fluoxetine Shows Antiviral Activity Against the Novel Variants in vitro.
Introduction: A common RBD mutation, N501Y, is shared by alpha, beta, and gamma, while K417N and E484K are found in beta and gamma.
Introduction: Moreover, infection by pseudotyped viruses carrying N501Y, K417N, or E484K single point mutations or triple mutation (N501Y/K417N/E484K) in the spike protein was shown to be reduced by fluoxetine.
Result: We found that fluoxetine (10 microM) treatment for 24 h was effective against pseudotyped viruses carrying single point mutations in their S protein (N501Y, PMID: 35140714
2021
Frontiers in immunology
Result: By contrast, N501Y slightly strengthens the binding, establishing a hydrogen bond with D57 in CDRH2 ( Figure 4B ).
SARS_CoV_2 mutation literature information.
PMID: 
2021
Journal of clinical microbiology
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