Abstract: Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and <
Introduction: Lineage P.1 contains 10 lineage-defining amino acid mutations in the virus spike protein (L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, H655Y, and T1027I) compared with its immediate ancestor (B.1.1.28).
Introduction: The same three residues are mutated with the B.1.351 variant of concern, and N501Y is also present in the B.1.1.7 lineage.
Polysulfates Block SARS-CoV-2 Uptake through Electrostatic Interactions*.
PMID: 33860605
2021
Angewandte Chemie (International ed. in English)
Abstract: Furthermore, in molecular dynamics simulations, we verified that LPGS can bind more strongly to the spike protein than heparin, and that LPGS can interact even more with the spike protein of the new N501Y and E484K variants.
Introduction: Moreover, we investigate the consequences of the N501Y and E484K mutations in the spike protein for the virus binding to HS.
Introduction: [22] The N501Y variant is reported to be more infectious than the wild-type virus, and a virus carrying this mutation was adapted to infect mice, which cannot be infected by wild-type SARS-CoV-2.
Result: From the total number of contacts (Figure 5 f, inset) and interaction energies (Figure 5 e), we found that LPGS bi
Conclusion: It is evident that the SARS-CoV-2 variants pose an international health risk, the mutations of E484K and N501Y are the two most implicated mutations.
Introduction: A study of the genome of this B.1.351 variant has revealed very similar mutations to those present in the P.1 Brazilian strain, namely mutations of E484K and N501Y glycoproteins are present.
Introduction: At this current stage the South African variant B.1.351 poses the greatest risk to international health as it is the most widespread, most resistant to current vaccinations and harbours both the E484K and N501Y mutations.
Introduction: It is thus evident that the P.1 strain has the mutations of both E484K and N501Y making
Emergence in southern France of a new SARS-CoV-2 variant harbouring both N501Y and E484K substitutions in the spike protein.
PMID: 33881861
2021
The journal of physical chemistry. B
Abstract: A recently identified variant of SARS-CoV-2 virus, known as the United Kingdom (UK) variant (lineage B.1.1.7), has an N501Y mutation on its spike protein.
Abstract: Here, we report an efficient computational approach, including the simple energy minimizations and binding free energy calculations, starting from an experimental structure of the binding complex along with experimental calibration of the calculated binding free energies, to rapidly and reliably predict the binding affinities of the N501Y mutant with human ACE2 (hACE2) and recently reported miniprotein and hACE2 decoy (CTC-445.2) drug candidates.
Abstract: It has been demonstrated that the N501Y mutation markedly increases the ACE2-spike protein binding affinity (Kd) from 22 to 0.44 nM, which could partially explain why the UK variant is mo
Vaccine Breakthrough Infections with SARS-CoV-2 Variants.
PMID: 33882219
2021
The New England journal of medicine
Discussion: In January 2021, Moderna announced clinical efforts to target a new variant of SARS-CoV-2 that was first identified in South Africa and includes three mutations (E484K, N501Y, and K417N) in the angiotensin-converting-enzyme 2 receptor-binding domain.
Mutations in the SARS-CoV-2 spike protein modulate the virus affinity to the human ACE2 receptor, an in silico analysis.
Discussion: Additionally, as recently reported, the host antibodies generated after vaccination with the currently available mRNA vaccine could neutralize the N501Y variant (Xie et al., 2021).
Discussion: In the most prevalent mutants such as N501Y and B.1.1.7, the substitution of Asp to Tyr resulted in a substantial conformational reorganization that led to an increased number of interactions and changed nature of these interactions between the spike protein and ACE2 receptor.
Discussion: Recently, the scientific and health community also has focused on the new variants called the South African (B.1.351) and Brazilian (P.1) variants that carry several mutations including both the N501Y and E484K (Tang et al., 2021; Toovey et al., 2021).
Discussion: The binding free energy of this mutant to ACE2 is low
Abstract: Here, we report the near-complete genome sequence and the genetic variations of a clinical sample of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) harboring the N501Y mutation assigned to the B.1.1.7 lineage.
Introduction: The spike gene carries the mutation known as N501Y (Asn501Tyr; c.1501A>T).
Table: p.Asn501Tyr
Emergence in southern France of a new SARS-CoV-2 variant harbouring both N501Y and E484K substitutions in the spike protein.
Introduction: N501 is one of six key contact residues within the RBD, and the N501Y mutation increases binding affinity to human and mouse ACE2.
Introduction: Nanobody-Fc fusions effectively blocked ACE2 receptor engagement with naturally occurring RBD variants present in human populations, showed potent neutralization against wild-type (WT) SARS-CoV-2 and an N501Y D614G variant, and, when used prophylactically, protected mice infected with a SARS-CoV-2 N501Y D614G variant.
Introduction: Within the RBD, B.1.1.7 carries N501Y mutation; B.1.351 carries K417N, E484K, and
Combined RT-qPCR and pyrosequencing of a Spike glycoprotein polybasic cleavage motif can uncover pediatric SARS-CoV-2 infections associated with heterogeneous presentation.
PMID: 33893880
2021
Molecular and cellular pediatrics
Result: Remarkably, N501Y was seen in 2 other adult samples (Figure S7), but neither E484K nor P681H (data not shown).
Result: Using different sequencing primers (Table S1), we could not detect N501Y in the P681H sample, which is a key substitution for 3 variants-of-concern.
Discussion: In contrast, genotyping by pyrosequencing alone seems inprecise, since the solitary occurrence of N501Y or P681H is not sufficient for the detection of the currently emerging variants-of-concern.
Overcoming Culture Restriction for SARS-CoV-2 in Human Cells Facilitates the Screening of Compounds Inhibiting Viral Replication.
PMID: 33903110
2021
Antimicrobial agents and chemotherapy
Discussion: Mutation E484D very often emerges during cell culture of SARS-CoV-2 (in both Vero E6 and human cells), versus E484K, which has been found in infected individuals, usually combined with N501Y.