SARS_CoV_2 mutation literature information.


  Emerging vaccine-breakthrough SARS-CoV-2 variants.
 PMID: 34518803       2021       ArXiv
Introduction: By analyzing the frequency, binding free energy (BFE) changes, and antibody disruption counts of RBD co-mutations, we reveal that nine RBD co-mutation sets, namely [L452R, T478K], [L452Q, F490S], [E484K, N501Y], [F490S, N501Y], [S494P, N501Y], [K417T, E484K, N501Y], [K417N, L452R, T478K], [K417N,


  In vitro selection of Remdesivir resistance suggests evolutionary predictability of SARS-CoV-2.
 PMID: 34534263       2021       PLoS pathogens
Method: The receptor binding domain of Spike is from amino acids 319-541: B1.351 and P1 had 3 mutations in the RBD (K417N/T, E484K and N501Y) while Alpha (B.1.1.7) only had one (N501Y).
Method: We used the following amino acids replacements and deletions in Spike for each lineage-based COG-UK defined changes for each lineage; Beta (B1.351; L18F, D80A, D215G, R246L, K417N, E484K, N501Y, A701V), Gamma (P.1;


  Contribution of single mutations to selected SARS-CoV-2 emerging variants spike antigenicity.
 PMID: 34536797       2021       Virology
Introduction: Similarly, the E484K and K417N/T mutations in the RBD that were first described in the B.1.351 and P.1 lineages likely due to immune evasion from vaccine or natural infection-elicited antibodies, are now present in several other lineages.
Result: Although both K417N and K417T presented a modest increase in the on-rate kinetic by ~1.56 and ~1.11 folds, the accelerated off-rate kinetics dictated the overall decrease affinity of these mutants.
Result: Interestingly, the RBD mutation K417


  Emergence in southern France of a new SARS-CoV-2 variant harbouring both N501Y and E484K substitutions in the spike protein.
 PMID: 34537136       2021       Cell
Introduction: Although both the K417N and K417T mutations can reduce the affinity of Spike for ACE2, in conjunction with the N501Y and E484K mutations, ACE2 binding is restored to that of wild-type Spike.


  The emergence and ongoing convergent evolution of the SARS-CoV-2 N501Y lineages.
 PMID: 34537136       2021       Cell
Introduction: K417N and K417T also both have moderately positive impacts on Spike expression, and these and other mutations at S/417 provide modest protection from neutralization by some convalescent sera, vaccine-induced antibodies, and some neutralizing monoclonal antibodies.
Introduction: Whereas V2 sequences generally carry a K417N mutation, V3 sequences carry a K417T mutation.
Result: In this regard, while mutations at S/20, S/80, S/138, S/215, and S/570 in different lineages do not predominantly converge on the same encoded amino acid states, they could nevertheless still be convergent on similar fitness objectives (immune escape or compensation for the fitness costs of other mutations): such as is likely the case with the also not strictly convergent V2


  Receptor binding, immune escape, and protein stability direct the natural selection of SARS-CoV-2 variants.
 PMID: 34543625       2021       The Journal of biological chemistry
Discussion: For example, the triple mutant K417T/E484K/N501Y (Gamma variant) poses a serious threat with many factors, increased protein expression, increased activity and increased antibody escape potential favoring its emergence and persistence.
Discussion: For example, when the data in Table 5 is compared between the N501Y (Alpha variant), the triple mutant K417T/E484K/N501Y (Gamma variant) and the Wild-type, increase in ACE2 binding might be significantly determined by the N501Y mutation, since no significant differences were observed in the Kd of ACE2 binding between the N501Y and K417T/E484K/


  Review of the mechanisms of SARS-CoV-2 evolution and transmission.
 PMID: 34545334       2021       ArXiv
Introd
Introduction: A list of vaccine-escape (vaccine-breakthrough) mutations was tabulated in our early work, including S494P, Q493L, K417N, F490S, F486L, R403K, E484K, L452R, K417T, F490L, E484Q, and A475S.
Introduction: Indeed, Eli Lilly mAbs were taken off the market in March due to Beta [K417N, E484K, N501Y] and Gamma [K417T, E484K, N501Y] variants.


  The in vitro and in vivo efficacy of CT-P59 against Gamma, Delta and its associated variants of SARS-CoV-2.
 PMID: 34547629       2021       Biochemical and biophysical research communications
Introduction: In particular, three mutations (K417T, E484K, and N501Y) in RBD (Receptor Binding Domain) are common in Alpha (N501Y) and Beta (K417 N, E484K, and N501Y) which are associated with increased transmissibility, immune escape and pathogenicity.
Method: Mutant RBDs (K417T/E484K/N501Y, L452R/T478K, and L452R) were purchased from Sino Biological.
Method: Pseudoviruses for Gamma, Delta, Epsilon, Kappa,  PMID: 34549975       2021       Journal of virology
Table: K417T


  Discovery and Evaluation of Entry Inhibitors for SARS-CoV-2 and Its Emerging Variants.
 PMID: 34550770       2021       Journal of virology
Method: Mutation K417T in the P.1 variant was altered to K471N to generate the structure of the B.1.351 S-RBD variant using the Prime modeling program of Schrodinger Suite.



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