literature

SARS_CoV_2 mutation literature information.

E484K mutation in SARS-CoV-2 RBD enhances binding affinity with hACE2 but reduces interactions with neutralizing antibodies and nanobodies: Binding free energy calculation studies.

PMID: 34562851 2021 Journal of molecular graphics & modelling

Introduction: In the 501Y.V2 and 501Y.V3 variants, besides the N501Y mutation, two other mutations E484K and K417N (or K417T) occurred in RBD of the S protein, and it was revealed that the E484K mutation obviously enhances the binding affinity between RBD and hACE2.

Mutations of SARS-CoV-2 RBD May Alter Its Molecular Structure to Improve Its Infection Efficiency.

PMID: 34572486 2021 Biomolecules

Introduction: However, there have been several mutations reported in SARS-CoV-2 RBD, such as N501Y, L452R, S477N, E484K, A502S, N439K, S494P, T478K, K417N, and K417T.

Emergence and Spread of a B.1.1.28-Derived P.6 Lineage with Q675H and Q677H Spike Mutations in Uruguay.

PMID: 34578382 2021 Viruses

Introduction: The VOC P.1, which harbors the mutations of concern S:K417T/E484K/N501Y among its lineage defining mutations, originated in the Amazonas state in mid-November and rapidly spread across Brazil and to over 50 countries globally.

Variants of SARS-CoV-2, their effects on infection, transmission and neutralization by vaccine-induced antibodies.

PMID: 34604978 2021 European review for medical and pharmacological sciences

Abstract: S477N, E484K, Q677H, E484Q, L452R, K417T, K417N and N501Y.

Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 lineages circulating in Brazil.

PMID: 34615860 2021 Nature communications

Introduction: The coincident emergence of N501Y, K417T/N and E484K mutations in Gamma (P.1) and Beta (B.1.351) is suggestive of convergent evolution.

Introduction: Whilst P.2 harbours no other lineage-specific spike mutations, Gamma (P.1) has additional RBD mutations, most notably K417T and N501Y.

Method: Custom Gamma (P.1) and Zeta (P.2) ASP assays were designed to identify lineage-specific and highly sensitive single-nucleotide polymorphisms (SNPs) S:K417T (Gamma, P.1) and ORF1a:L3468V (Zeta, P.2).

Evaluation of the clinical and analytical performance of the Seegene allplex SARS-CoV-2 variants I assay for the detection of variants of concern (VOC) and variants of interests (VOI).

PMID: 34628158 2021 Journal of clinical virology

Introduction: Two subsequent variants of concern, B.1.351 (beta variant), first identified in South Africa, and P.1 (gamma variant), first identified in Brazil, were found to harbor the D614G and N501Y mutations, as well as 2 additional key mutations in the receptor binding domain (RBD), K417N/T and E484K, which increase binding affinity to the ACE2 receptor.

Table: K417T

Cross-Neutralizing Activity Against SARS-CoV-2 Variants in COVID-19 Patients: Comparison of 4 Waves of the Pandemic in Japan.

PMID: 34631915 2021 Open forum infectious diseases

Introduction: It bears 12 mutations in the spike gene, including K417T, E484K, and N501Y, which are the same 3 amino acid substitutions found in B.1.351.

Discussion: On the other hand, because P.1 and B.1.351 have similar mutations in their RBD (including E484K, K417T/N, and N501Y), it might be thought that the neutralization of both variants would be affected similarly.

Single domain shark VNAR antibodies neutralize SARS-CoV-2 infection in vitro.

PMID: 34637549 2021 FASEB journal

Discussion: The clusters share some of the mutations linked with viral escape, including N501Y (Alpha, Beta, and Gamma), E484K (Beta and Gamma) and K417N/T (Beta and Gamma).

SARS-CoV-2 Virus-Host Interaction: Currently Available Structures and Implications of Variant Emergence on Infectivity and Immune Response.

PMID: 34639178 2021 International journal of molecular sciences

Discussion: Mutation K417T deletes a salt bridge with D30 from hACE2, potentially leading to a decreased affinity.

Discussion: One of the defining characteristics of this variant is the high number of mutations, particularly in the spike protein, with three mutations specific to the RBD (K417T, E484K and N501Y), that lead to a 19-fold increase in affinity compared to the Wuhan strain.

Molecular rationale for SARS-CoV-2 spike circulating mutations able to escape bamlanivimab and etesevimab monoclonal antibodies.

PMID: 34642465 2021 Scientific reports

Abstract: The main findings from this study show that, compared to the wild-type SARS-CoV-2 spike protein, mutations E484A/G/K/Q/R/V, Q493K/L/R, S494A/P/R, L452R and F490S are predict

Discussion: In agreement with this and other evidences, our current computational alanine/mutagenesis study marks K417 and all its reported variants (K417E/N/R/T) as the strongest hot spots in eliciting potential escape to the LY-CoV016 mAb.

Discussion: Of note, the K417N and K417T in particular are spike MOIs in the SARS-CoV2 VOC lineages B.1.351 (Beta) and P.1 (Gamma), respectively.

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