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).
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.
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.
Result: As such, it is not surprising that replacing K417 on the viral protein with each of the alternative circulating mutants (K417E/N/R/T) reflects into a very strong interface disrupting behavior, with the exception of the substitution K417R, for which our in silico mutagenesis data anticipate a neutral effect.
Result: As such, the variation in bi
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.
The evolution of the mechanisms of SARS-CoV-2 evolution revealing vaccine-resistant mutations in Europe and America.
3Introduction: Moreover, we have pointed out that Y449S and Y449H are two vaccine-resistant mutations, and ""Y449S, S494P, K417N,
Introduction: Later on, we have provided a list of most likely vaccine escape RBD mutations with high frequency, including S494P, Q493L, K417N, F490S, F486L, R403K, E484K, L452R, K417T, F490L, E484Q, and A475S.
Genomic surveillance of SARS-CoV-2 tracks early interstate transmission of P.1 lineage and diversification within P.2 clade in Brazil.
Introduction: In addition to E484K, P.1 harbors the N501Y and K417T mutations in the RBD region.
Result: We found 16 SNVs targeting the receptor-binding domain (RBD) in S1, of which eight were missense variants, including K417T, N439K, L452R, S477R, E484K, N501Y, L518I, A522V.
Ten emerging SARS-CoV-2 spike variants exhibit variable infectivity, animal tropism, and antibody neutralization.
Result: K417N/T and N501Y also cause minor changes in local structure, which further weakens the affinity between CDRL and RBD, especially Y503 on RBD.
Result: K417N/T destroys the salt bridge, thus reducing the affinity significantly.
Result: Additionally, the K417N/T mutation caused reduced neutralization activity involving five mAbs (1F9, 2H10, 10D12, CB6, and A247), whereas it increased the neutralization sensitivity of one mAb (A261-262) for more than ten times.
Result: Furthermore, the neutralization activity against the K417T/N single-mutation strain was increased among all serum samples.
Result: Single mutation analyses showed that K417T, PMID: 34649268
2021
Nature
Introduction: These include the VOCs B.1.351/Beta and P.1/Gamma, which carry the spike variant N501Y that is also found in B.1.1.7/Alpha and a similar pair of mutations (K417N/T and E484K) that were each shown to reduce the binding affinity of antibodies from vaccine-derived or convalescent sera .
Comprehensive mapping of binding hot spots of SARS-CoV-2 RBD-specific neutralizing antibodies for tracking immune escape variants.
Introduction: Among the SARS-CoV-2 variants of concern, Beta B.1.351 (RBD-K417N/E484K/N501Y) discovered in South Africa and Gamma P.1 (RBD-K417T/E484K/N501Y) discovered in Brazil have been demonstrated to have high potential to reduce the efficacy of some vaccines.
Discussion: The valuable information that K417 are essential for multiple prototype VH3-53/3-66 NAb recognition allows us to re-interpret the potential significance of the mutation K417N and K417T present in B.1.351 and P.1.
SARS_CoV_2 mutation literature information.
PMID: 
2021
Journal of clinical virology
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