literature

SARS_CoV_2 mutation literature information.

Breadth of SARS-CoV-2 Neutralization and Protection Induced by a Nanoparticle Vaccine.

PMID: 35118474 2022 bioRxiv

Method: D614G spike mutation: D614G; Alpha (B.1.1.7) spike mutations: Delta69-70, Delta144, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H; Beta (B.1.351) spike mutations: L18F, D80A, D215G, Delta242-244, R246I, K417N, E484K, N501Y, D614G, A701V; Delta (B.1.61

SARS-CoV-2 Variants Associated with Vaccine Breakthrough in the Delaware Valley through Summer 2021.

PMID: 35130727 2022 mBio

Introduction: Some of the substitutions in these variants have been detected arising independently on multiple genetic backgrounds, such as the spike substitutions N501Y, E484K or the 69-70 deletion, supporting a model of convergent evolution.

Result: Two other closely studied spike substitutions, E484K and L452R, were not notably enriched among vaccine breakthrough cases, and the D253G substitution was modestly depleted.

Emerging Vaccine-Breakthrough SARS-CoV-2 Variants.

PMID: 35133792 2022 ACS infectious diseases

Introduction: By analyzing the frequency, binding free energy (BFE) changes, and antibody disruption counts of RBD comutations, we reveal that nine RBD comutation sets, namely [L452R, T478K], [L452Q, F490S], [E484K, N501Y], [F490S, N501Y], [S494P, N501Y], [K417T, E484K, N501Y], [K417N, L452R, T478K], [K417N,

Structural and biochemical rationale for enhanced spike protein fitness in delta and kappa SARS-CoV-2 variants.

PMID: 35136050 2022 Nature communications

Introduction: The S protein E484Q mutation in the Kappa variant was similarly found in the Beta (B.1.351) and Gamma (P.1) lineages, where residue 484 is mutated to lysine (E484K).

Result: We have previously demonstrated the sensitivity of ab8 and S2M11 to the E484K mutation, wherein both antibodies were fully escaped.

Figure: The K484 surface potential was generated using the previously reported D614G + N501Y + E484K focus-refined atomic model.

Final Analysis of Efficacy and Safety of Single-Dose Ad26.COV2.S.

PMID: 35139271 2022 The New England journal of medicine

5Result: Vaccine efficacy against severe-critical Covid-19 was 93.1% (95% CI, 54.4 to 99.8) for the reference strain; 71.8% (95% CI, 56.3 to 82.3) for non-reference strain SARS-CoV-2 lineages, including ""other"" sequences with the E484K mutation; 78.4% (95% CI, 34.5 to 94.7) for the beta variant; 63.6% (95% CI, 18.8 to 85.1) for the gamma variant; 67.6% (95% CI, -29.8 to 94.4) for the lambda variant; and 79

8Discussion: Efficacy against severe-critical disease remained higher (74.6%) than efficacy against moderate to severe-critical disease, with a lower point estimate for variants (93.1% efficacy against the reference strain and 71.8% efficacy against non-reference strain lineages, including ""other"" sequences with the E484K mutation), indicating that Ad26.COV2.S induces higher levels of protection in proportion to the severity of the disease and the nature of the viral mutation."

Prolonged SARS-CoV-2 RNA shedding in a young man recovering from traumatic pneumothorax.

PMID: 35139987 2022 South African medical journal

Abstract: Genotyping revealed canonical beta-variant E484K and N501Y mutations at earlier time points.

SARS-CoV-2 E484K Mutation Narrative Review: Epidemiology, Immune Escape, Clinical Implications, and Future Considerations.

PMID: 35140483 2022 Infection and drug resistance

Abstract: E484K has rapidly emerged and has frequently been detected in several SARS-CoV-2 variants of concern.

Abstract: In this study, we review the epidemiology and impact of E484K, its effects on neutralizing effect of several monoclonal antibodies, convalescent plasma, and post-vaccine sera.

Conclusion: E484K can be selected when a culture recombinant virus expressing SARS-CoV-2 S is treated with antibody cocktails, and new variants with novel mutations are on the rise.

In silico analysis of mutant epitopes in new SARS-CoV-2 lineages suggest global enhanced CD8+ T cell reactivity and also signs of immune response escape.

PMID: 35149224 2022 Infection, genetics and evolution

Abstract: Moreover, individual mutations such as Spike N501Y and Nucleocapsid D138Y were predicted to have an overall stronger affinity through HLA-I than the reference sequence while Spike E484K shows signs of evasion.

Result: In contrast, peptides derived from E484K exhibited weaker binding compared to the respective REF-derived peptides.

Table: E484K

Conformational Flexibility and Local Frustration in the Functional States of the SARS-CoV-2 Spike B.1.1.7 and B.1.351 Variants: Mutation-Induced Allosteric Modulation Mechanism of Functional Dynamics and Protein Stability.

PMID: 35163572 2022 International journal of molecular sciences

Introduction: S-B.1.351 variant is characterized by 21 mutations with 9 mutations (L18F, D80A,

Method: A systematic mutational scanning and sensitivity analysis of the functional RBD residues (K417, E484, N501), S-B.1.1.7 mutational sites (N501Y, A570D, P681H, T716I, S982A, and D1118H) and S-B.1.351 mutational sites (L18F, D80A, D215G, K417N, E484K, N501Y, D614G, and A701V).

SARS-CoV-2 Variants Increase Kinetic Stability of Open Spike Conformations as an Evolutionary Strategy.

PMID: 35164561 2022 mBio

Result: 1C); E484K was later adopted by the Alpha variant after the emergence of the Beta and Gamma variants.

Result: E484K and N501Y reside in the RBM of spike that directly contacts the receptor hACE2.

Result: E484K substitution exhibited a noticeable effect of reducing the occupancy of ligand-free spike variant in the 0.5-FRET state and increasing the 0.3-FRET state occupancy.

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