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.
Epitope Classification and RBD Binding Properties of Neutralizing Antibodies Against SARS-CoV-2 Variants of Concern.
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
Expansion of L452R-Positive SARS-CoV-2 Omicron Variant, Northern Lombardy, Italy.
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 virus pseudotyped with the parental SARS-CoV-2
SARS_CoV_2 mutation literature information.
PMID: 
2021
Infection, genetics and evolution
Browser Board
Co-occurred Entities
Filtrator
ViMRT