Structure-Function Analysis of Resistance to Bamlanivimab by SARS-CoV-2 Variants Kappa, Delta, and Lambda.
PMID: 34648284
2021
Journal of chemical information and modeling
Introduction: Similarly, the N501Y mutation found in the B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.1.28.1 (Gamma) variants has been demonstrated to increase the binding affinity between the receptor-binding domain (RBD) and its human receptor ACE2 (hACE2), making these variants more transmissible.- Moreover, experimental and computational studies have showed that K417N and E484K found in the Beta variant could evade neutralization by many monoclonal antibodies (mAbs).
Discussion: It is worth noting that the recent sub-lineage of B.1.617 (dubbed as Delta+) contains the K417N mutation, allowing the virus to escape LY-CoV016 as well.
In vivo characterization of emerging SARS-CoV-2 variant infectivity and human antibody escape potential.
Abstract: Immune escape of the K417N + E484K variant is observed because infection can be appreciated in the nasopharynx, but not lungs, of mice transferred with low-antibody-tier plasma.
Abstract: We utilize N501Y to survey in vivo pseudovirus infection dynamics and susceptibility to reinfection with the L452R (Los Angeles), K417N + E484K (South Africa), and L452R + K417N + E484Q (India) variants.
Method: 24-hours later, normalized amounts of WT (no 19del), WT, D614G, N501Y (no 19del), N501Y
Genomic reconstruction of the SARS-CoV-2 epidemic in England.
Introduction: The AY.1 lineage, derived from Delta and containing an additional K417N mutation, appeared only transiently.
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.
Abstract: Furthermore, we showed that RBD co-mutations K417N, E484K, and N501Y present in B.1.351 appear more resistant to NAbs and human convalescent plasma from the early stage of the pandemic, possibly due to an additive effect.
Abstract: The comprehensive escape mutation map not only confirms th
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.
Spike protein evolution in the SARS-CoV-2 Delta variant of concern: a case series from Northern Lombardy.
Discussion: AY.2 additionally harbours V70F (unique among delta lineages), A222V (shared with AY.9, AY.10, AY.11, AY.19 and AY.24) and K417N (as for AY.1) K356N and V1228L have also been rarely reported.
The evaluation of potential global impact of the N501Y mutation in SARS-COV-2 positive patients.
Introduction: On the other hand, in B.1.351 lineage, the K417N, and E484K mutations are found in the RBD region.
Result: Sequence alignment of RBD from SARS-CoV-2, B.1.1.7, and B.1.351 variants spike proteins are (the N501Y, K417N, and E484K mutations) shown in red with circle.
In Vitro Effect of Taraxacum officinale Leaf Aqueous Extract on the Interaction between ACE2 Cell Surface Receptor and SARS-CoV-2 Spike Protein D614 and Four Mutants.
Introduction: Free energy perturbation calculations for interactions of the N501Y and K417N mutations with both the ACE2 receptor and an antibody derived from COVID-19 patients raise important questions about the possible human immune response and the success of already-available vaccines.
Introduction: Here we report on the inhibitory potential of dandelion on the binding of the spike S1 protein RBD to the hACE2 cell surface receptor and compare the effect of the original D614 spike protein to its D614G, N501Y, and mix (K417N, E484K, and N501Y) mutations.
Introduction: The Beta variant contai
Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant-dependent manner.
Method: SARS-CoV-2 pseudotyped lentiviruses were prepared by co-transfecting the HEK293T cell line with either the SARS-CoV-2 ancestral variant spike (D614G), the Beta spike (L18F, D80A, D215G, K417N, E484K, N501Y, D614G, A701V, 242-244 del) or the Delta spike (T19R, R158G L452R, T478K, D614G, P681R, Table: K417N
Emerging SARS-CoV-2 variants expand species tropism to murines.
Result: 1e-g), suggesting the K417N/T and E484K mutation in the RBD of these variants might further facilitate mouse adaptation in addition to the N501Y substitution.
Discussion: Apart from the N501Y mutation, several amino acid substitutions including K417N, E484K, Q493H/K, and Q498H were also suggested to be critical for SARS-CoV-2 adaptation in murine species.
Discussion: This is congruous with our observation that B.1.351 replicated to a higher level than B.1.1.7 and P.3 in wildtype mice since B.1.351 carries K417N, E484K in addition to N501Y.
Functional Effects of Receptor-Binding Domain Mutations of SARS-CoV-2 B.1.351 and P.1 Variants.
Result: The K417N ( Figure 4A ) and K417T mutants ( Figure 4B ) had no noticeable effect.
Result: The K417N:but not the K417T:appeared to be inhibited better than the wt.
Result: We observed a 1.9- and 1.5-fold reduction in the median inhibition of the E484K and N501Y RBD compared to the wt, while the substitutions in the 417 position had puzzlingly opposite effects with apparent 1.4- and 1.2-fold inhibition gain for K417N and K417T, respectively (Friedman test p < 0.0001 for all).
Result: When comparing the inflection temperatures (Ti) of the single RBD mutations with their wt counterpart, we observed a destabilizing
SARS_CoV_2 mutation literature information.
PMID: 
2021
Journal of chemical information and modeling
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