Discussion: Although there are many factors governing viral evolution, these results suggest that the independent evolution of L452R-bearing spikes and N501Y-, K417N/T-, and E484K-bearing spikes may be explained by a lack of synergistic increase in ACE2 binding upon combination of these mutations.
Discussion: Although these mutational combinations enable enhanced ACE2 binding compared with wild-type spikes, the increase in ACE2 binding affinity conferred by the L452R mutation in isolation was not preserved.
Discussion: As L452 is distal to the ACE2-RBD interface, it has been previously suggested that the L452R mutation may increa
Glycan Masking of Epitopes in the NTD and RBD of the Spike Protein Elicits Broadly Neutralizing Antibodies Against SARS-CoV-2 Variants.
Introduction: The Delta (B.1.617.2) variant encodes an S protein with ten mutations (T19R, G142D, del 156, del 157, R158G, L452R, T478K, D614G, P681R, and D950N), two of which are in the RBD (L452R and T478K).
Introduction: The immunity-evading mutations in the Beta (B1.351) variant include E484K in the RBD of the S protein, while those in the Delta (B.167.2) variant include L19R, del 157, del 158, L452R
The Development of SARS-CoV-2 Variants: The Gene Makes the Disease.
PMID: 34940505
2021
Journal of developmental biology
Introduction: L452R, defined as an escape mutation, has been shown to promote a much higher viral replication in non-human cell cultures, which would correspond with the better fitness of the Delta variant observed in populations.
Introduction: It is characterized by the L452R mutation, which was expected to give an advantage when spreading over other variants, being more contagious than earlier forms.
Introduction: The ancestral lineage B.1.617 is not a variant but a cluster of sequences within clade G that share the common signature mutations: G142D, L452R, E484Q, D614G, and P681R.
Introduction: The substitution L452R can impair neutralization by several nAbs and convalescent plasma and emerge
Insights into the Binding of Receptor-Binding Domain (RBD) of SARS-CoV-2 Wild Type and B.1.620 Variant with hACE2 Using Molecular Docking and Simulation Approaches.
Introduction: In contrast, the delta+ variant acquired an additional mutation, the K417N mutation, alongside the L452R and T478K mutations.
Introduction: The Kappa (kappa) variant, also known as B.1.617.1, first identified in India, and designated as a VOI, owns a single mutation, that is, L452R, which was suspected to be associated with reduced antibody neutralization by disrupting the respective conformational epitopes.
Introduction: To date, many variants have been reported, among which the VOC Delta (delta)+ (AY.1 or lineage B.1.617.2.1), which evolved from Delta, demonstrated a different mutational landscape by acquiring L452R and T478K mutations in the RBD.
Computational Saturation Mutagenesis of SARS-CoV-1 Spike Glycoprotein: Stability, Binding Affinity, and Comparison With SARS-CoV-2.
PMID: 34957216
2021
Frontiers in molecular biosciences
Result: Recent SARS-CoV-2 variant L452R ( G = -0.395 kcal/mol; G = 0.021 kcal/mol) corresponds to SARS-CoV-1 K439R ( G = 0.247 kcal/mol; G = 0.41 kcal/mol).
Result: The change in residue from Lysine in SARS-CoV-1 S protein to Leucine in SARS-CoV-2 S protein may be responsible for the increase in binding affinity caused by L452R.
SARS-CoV-2 Delta Variant Displays Moderate Resistance to Neutralizing Antibodies and Spike Protein Properties of Higher Soluble ACE2 Sensitivity, Enhanced Cleavage and Fusogenic Activity.
Result: A further reduction in neutralization titers was seen against pseudoviruses bearing both L452R and T478 substitutions in RBD displayed (GMT 192) compared to WT(D614G) (GMT 392).
Result: A prior study showed that convalescent sera and vaccine-elicited antibody neutralization titers against pseudoviruses bearing spikes containing L452R-E484Q-P681R substitutions displayed 2-5-fold reduction, compared to the neutralization titers against WT(D614G) pseudoviruses.
Introduction: The latest variant of concern, variant Delta (lineage B.1.617.2, clades 21A, 21I and 21J), emerged in India in October 2020 and was later detected in France in May 2021, and has the L452R mutation that makes it more transmissible.
Discussion: Interestingly, K417N, L452R, E484K, and E484Q are the mutations known to disrupt receptor-binding domain (RBD) binding capacity, making them more infectious by immune escape against the current vaccines.
Discussion: The variant belonging to the lineage B1.617.2 was shown to be resistant to the mAb bamlanivimab due to the escape mutation L452R and was also less sensitive to sera from convalescent patients.
A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants.
Introduction: The Delta variant contains the unique L452R and T478K mutations while sharing a common mutation with the Alpha and Gamma variants at P681 near the furin cleavage site.
SARS-CoV-2 Variants: Mutations and Effective Changes.
PMID: 34975266
2021
Biotechnology and bioprocess engineering
Abstract: Certain mutations (D614G, E484K, N501Y, K417N, L452R and P681R) have appeared across several different strains, often accompanied by others that may be complementary working together to confer increased infectivity, fitness, or resistance to neutralization.
Analysis of Clinical Characteristics and Virus Strains Variation of Patients Infected With SARS-CoV-2 in Jiangsu Province-A Retrospective Study.