Emergence in southern France of a new SARS-CoV-2 variant harbouring both N501Y and E484K substitutions in the spike protein.
PMID: 33991677
2021
Clinical microbiology and infection
Abstract: RESULTS: We identified that SARS-CoV-2 genomes from four patients diagnosed in our institute harboured a new set of amino acid substitutions including L18F, L452R,
Introduction: These variants include the Marseille-4 variant (Nexstrain clade 20A.EU1), which has been the most prevalent one between August 2020 and January 2021, and the rapidly-spreading variants 20I/501Y.V1, 20H/501Y.V2, and 20J/501Y.V3, which harbor in their spike the amino acid (aa) substitution N501Y.
Figure: Map of the nucleotide and aa substitutions and deletions of the new variant along the SARS-CoV-2 genome (a) and three-dimensional structure of the spike protein showing aa substitutions and deletions in various spike N501Y variants (b).
Structural Modeling of the SARS-CoV-2 Spike/Human ACE2 Complex Interface can Identify High-Affinity Variants Associated with Increased Transmissibility.
Discussion: Interestingly, our models predict that the triple mutation K417T/E484K/N501Y, which arose in the ancestral lineage E484K/N501Y, has about the same affinity as WT, although its frequency is increasing around the globe.
Discussion: Our analysis also predicts that the unobserved triple mutant S477N/E484K/N501Y has the highest affinity among all combinations of fast-spreading mutations examined.
Discussion: Our structural analysis suggests that the widespread N501Y mutation likely introduces stabilizing cation-pi interactions between S Y501 and hACE2 K353, whereas E484K enhances the solvatio
Q493K and Q498H substitutions in Spike promote adaptation of SARS-CoV-2 in mice.
Discussion: Several mouse-adapted SARS-CoV-2 strains, such as MASCp6 (N501Y), MA10 (Q493K) and HRB26 (Q498H), increase virulence or replication in mice likely attributed to one of the mutations in the S protein.
Discussion: The mutations N501Y, Q493K, or Q498H were predicted to enhance interactions with the mACE2 receptor.
Vaccine-escape and fast-growing mutations in the United Kingdom, the United States, Singapore, Spain, India, and other COVID-19-devastated countries.
Result: , four ACE2 binding-strengthening mutations have a rapid growth since late December 2020: N501Y, K417N, E484K, and P479S.
Result: 13 , shows that, in addition to well-known mutations E484K, K417N, and N501Y, mutations N439K, L452R, S477N, S477R, and N501T are also ACE2 binding-strengthening mutations that have a high growth rate recently with high frequency.
Result: ACE2 binding-strengthening mutations in India include N440K, L452R, E484Q,
Mutation-Specific SARS-CoV-2 PCR Screen: Rapid and Accurate Detection of Variants of Concern and the Identification of a Newly Emerging Variant with Spike L452R Mutation.
PMID: 34011523
2021
Journal of clinical microbiology
Abstract: The screening results were compared to the whole-genome sequencing (WGS) and showed 100% concordance for strain typing for B.1.1.7 (n = 25) and P.1 (n = 5) variants using spike (S) mutation S-N501Y, S-E484K, and S-H69-V70del assays.
Novel SARS-CoV-2 variants: the pandemics within the pandemic.
PMID: 34015535
2021
Clinical microbiology and infection
3Introduction: Search terms used in various combinations were as follows: ""SARS-CoV-2"", ""variants"", ""variants of concern"", ""VOC"", ""variants of interest"", ""VOI"", ""mutations"", ""evolution"", ""B.1.1.7"", ""B.1.351"", ""P.1"", ""B.1.148"", ""B.1.1.28"", ""N501Y"", ""E484K"", and ""L452R""."
Abstract: The N501Y mutation is shared by the three main VOCs: B.1.1.7, first identified in the United Kingdom, P.1, originating from Brazil, and B.1.351, first described in South Africa.
Method: B.1.621 has been identified in Columbia as having a similar mutation profile (E484K and N501Y) as the VOCs B.1.351 and P.1, but is from a distinct lineage.
Method: HMN.19B - Henri Mondor 19B variant identified in France: Very little information is available about this variant,
Genomic epidemiology of SARS-CoV-2 in Esteio, Rio Grande do Sul, Brazil.
Introduction: The genetic diversity of SARS-CoV-2 has been extensively studied, evidencing the presence of recurrent mutations such as S: D614G, S:E484K, S:N501Y across the world, related to increased pathogenicity and transmissibility (higher viral loads, increased replication on lung epithelial cells, and enhanced binding affinity).
Discussion: Until mid-December 2020, 157 genomes have this mutation globally, 114 (72.6%) isolated from South Africa, where a new lineage (B.1.351 or 501Y.V2) characterized by three RBD mutations (K417N, E484K and N501Y) recently emerged.
Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants.
Introduction: Among 585,054 SARS-CoV-2 genome sequences in the GISAID database (March 5, 2021), about 95% of K417N/T mutations occur with N501Y, despite N501Y being present in only 21% of all analyzed sequences.
Introduction: Consistently, K417N/T mutations are associated with N501Y in naturally circulating SARS-CoV-2.
Introduction: Here, we quantified binding of K417N, E484K, N501Y, and double and triple combinations in the RBD to ACE2 by biolayer interferometry.
Introduction: Importantly, N501Y could rescue binding of K417N (9.0 nM), and the triple mutant
Humoral immune response to circulating SARS-CoV-2 variants elicited by inactivated and RBD-subunit vaccines.
Introduction: 501Y.V1 is associated with a set of mutations in its spike (S) protein, including DeltaH69/V70 and DeltaY144 in N-terminal domain (NTD), N501Y in receptor-binding domain (RBD), and P681H near the furin cleavage site.
Introduction: 501Y.V2 is associated with multiple S mutations, which could be divided into two main subsets, one is clustered in NTD (L18F, D80A, D215G, 242-244Delta, and R246I), and the other is clustered in RBD (K417N, E484K, and N501Y).|mgd
Experimental Evidence for Enhanced Receptor Binding by Rapidly Spreading SARS-CoV-2 Variants.
Result: Compared to the effect of N501Y, the effect of the single E484K mutation on binding affinity is minor (1.4-fold; Figure 1(F), table 1).
Result: Double mutant E484K/N501Y forms a slightly more stable complex with hACE2 than the N501Y single mutant (1.4 nM instead of 2.4 nM, Table 1, Figure 1(F)).
Result: Interestingly, while the increase in affinity for N501Y is due to decreased dissociation, increased affinity for E484K is accomplished through faster association.
Result: The change in affinity is predominantly caused by a reduction in the dissociation rate constant, indicating the N501Y spike protein remains bound to the receptor for a longer time
SARS_CoV_2 mutation literature information.
PMID: 
2021
Clinical microbiology and infection
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