RT-qPCR Assays for Rapid Detection of the N501Y, 69-70del, K417N, and E484K SARS-CoV-2 Mutations: A Screening Strategy to Identify Variants With Clinical Impact.
PMID: 34123874
2021
Frontiers in cellular and infection microbiology
Abstract: Methods: Targeting spike (S) gene mutations of SARS-CoV-2 (N501Y, 69-70del, K417N, and E484K), specific primers, and probes for three specific quantitative reverse transcription PCR (RT-qPCR) assays were designed, and validated using Sanger sequencing.|mg
Introduction: Four mutations (N501Y, 69-70del, K417N, and E484K) in the spike protein could explain the potential biological effects that have been described for these variants.
Introduction: Mutation N501Y has been found on the receptor-binding domain (RBD) and has been associated with an increase of binding affinity to the ACE2 receptor.
Rapidly emerging SARS-CoV-2 B.1.1.7 sub-lineage in the United States of America with spike protein D178H and membrane protein V70L mutations.
Abstract: It is defined by the N501Y mutation in the receptor-binding domain (RBD) of the Spike (S) protein, and a few other mutations.
Introduction: The Spike (S) protein N501Y mutation in the receptor-binding domain (RBD) confers higher binding affinity of the S protein for ACE2, while the other two deletions, HV69-70del and Y144del in the N-terminal domain (NTD) may also play a role in ACE2 receptor binding or neutralizing antibody escape.
Discussion: This is the same observed with other deleterious mutations like the N501Y and E484K
Rapid Increase of SARS-CoV-2 Variant B.1.1.7 Detected in Sewage Samples from England between October 2020 and January 2021.
Introduction: Amino acid substitutions at residue 417, K417N in B.1.351 and K417T in P.1, appear to improve evasion from antibodies in combination with N501Y and E484K.
Introduction: Mutation N501Y, located within the receptor-binding domain (RBD), can increase binding affinity to human and murine angiotensin-converting enzyme 2 (ACE-2) receptor and cell infectivity in mice.|mg
Figure: (A) Deletion of nucleotides 21765 to 21770 (deletion of amino acids HV69-70); (B) deletion of nucleotides 21991 to 21993 (deletion of amino acid Y144); (C) mutation A23063T (amino acid change N501Y); (D) mutation C23271A (amino acid change A570D).
Rapid and simultaneous identification of three mutations by the Novaplex SARS-CoV-2 variants I assay kit.
Abstract: Of them, two harbored both H69/V70 deletion and N501Y substitution, whereas two harbored E484K substitution alone.
Introduction: All three VOCs listed above harbor the N501Y mutation; B.1.1.7 harbors an additional H69/V70 deletion; and the other two, the E484K substitution mutation.
Introduction: Among the various mutations emerging in SARS-CoV-2, those in the spike (S) protein, specifically the H69/V70 deletion and E484K N501Y substitution mutations, are important because the S protein is involved in infectivity to host cells via angiotensin-converting enzyme 2 and the main target of neutralizing antibodies induced by vaccines.
Discussion: In Japa
Proliferation of SARS-CoV-2 B.1.1.7 Variant in Pakistan-A Short Surveillance Account.
Abstract: Based on the partial sequencing of SGTF samples 93.5% (n = 29/31) showed the characteristic N501Y, A570D, P681H, and T716I mutations found in the B.1.1.7 variant.
Result: Based on the partial sequencing of spike gene of SGTF samples, 93.5% (n = 29/31) showed the characteristic N501Y, A570D, P681H, and T716I mutations found in the B.1.1.7 variant.
Result: The age of patients infected with the N501Y variant ranged from 12 to 90 years with a median age of 32.5 years.
Result: The distribution of N501Y positive cases according to a geographic area is shown in Figure 2B.
Quantitative analysis of ACE2 binding to coronavirus spike proteins: SARS-CoV-2 vs. SARS-CoV and RaTG13.
PMID: 34137759
2021
Physical chemistry chemical physics
Abstract: Both calculations confirmed a significant increase of the binding affinity of the N501Y mutant to ACE2 and explained its molecular mechanism.
Abstract: We also calculated an important mutation of N501Y in SARS-CoV-2 using both alanine scanning calculation and a thermodynamic integration (TI) method.
Characterization of a new SARS-CoV-2 variant that emerged in Brazil.
Introduction: S protein plays a key role in viral binding to host cell receptors (i.e., human angiotensin-converting enzyme 2 [hACE2]), and the P.1 variant has three mutations (K417T, E484K, and N501Y) in the receptor-binding domain (RBD).
Introduction: Previous studies suggest that both the E484K and N501Y mutations in the RBD may enhance the binding affinity of the S protein for hACE2.
Result: However, studies have shown that the N501Y mutation in the RBD renders mice susceptible to SARS-CoV-2 infection.
Result: Taken together, these observation
An ACE2 Triple Decoy that neutralizes SARS-CoV-2 shows enhanced affinity for virus variants.
5Result: All but the construct expressing L452R/K417N showed higher affinity for ACE(WT) (Table S7 in the ""Supplementary Information S1""), which aligns with what might be predicted from the results in Table S5:K417N decreases affinity and N501Y increases affinity."
Result: 3s, inhibition in the surrogate virus neutralization assay modified to assess competition by the ACE2 Triple Decoy for ACE2 (WT) binding to S RBD was similar for S RBD WT, E484K, N501Y, L452R, and K417N/E484K/N501Y.
Recent progress on the mutations of SARS-CoV-2 spike protein and suggestions for prevention and controlling of the pandemic.
PMID: 34146731
2021
Infection, genetics and evolution
Abstract: Among these mutations, the most representative ones are substitution mutations such as D614G, N501Y, Y453F, N439K/R
Figure: Among these mutations, the most representative ones are substitution mutations such as D614G, N501Y, Y453F, N439K/R, P681H, K417N/T, and E484K, and deletion mutations of DeltaH69/V70 and Delta242-244.
Figure: Three mutations, D614G, N501Y, and E484K, confer the virus with enhanced infectivity, transmissibility, and resistance to neutralization.
Rational optimization of a human neutralizing antibody of SARS-CoV-2.
PMID: 34147856
2021
Computers in biology and medicine
Introduction:
Introduction: Experimental data suggests mutation N501Y increases the binding affinity of the spike protein with human and murine ACE2.
Introduction: It is estimated that the spread of SARS-CoV-2 N501Y variant is 70% faster than previous strains, indicating a much higher infectivity.
Introduction: N501 of RBD is spatially distant from its interacting interface with P2B-2F6, and thereby the newly identified mutation N501Y is unlikely to affect the neutralizing activity of P2B-2F6.
Introduction: These variants have an unusually large number of genetic changes, including the noteworthy spike protein mutation N501Y, one of the key residues in RBD domain interacting with ACE2.
SARS_CoV_2 mutation literature information.
PMID: 
2021
Frontiers in cellular and infection microbiology
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