Abstract: Recently, a new strain is reported in India that includes a mutation (T478K, and L452R) in the RBD, that is possibly increasing the infection rate.
Introduction: Besides, L452R mutation recently reported to enhance the viral replication by increasing the S protein stability and viral infectivity and viral fusogenicity.
Introduction: In contrary to T478K, the L452R variant is shown to enhance the total binding energy between RBD and ACE2 to be about 2.63 kcal/mol more negative than its value in WT protein.
Introduction: In this research, we study the effect of both of L452R and T478K variants in the
Development of an efficient Sanger sequencing-based assay for detecting SARS-CoV-2 spike mutations.
Abstract: Here, we developed five SARS-CoV-2 spike gene primer pairs (5-SSG primer assay; 69S, 144S, 417S, 484S, and 570S) and verified their ability to detect nine key spike mutations (DeltaH69/V70, T95I, G142D, DeltaY144, K417T/N, L452R, E484K/Q, N501Y, and H655Y) using a Sanger sequencing-based assay.
Loss of Neutralizing Antibody Response to mRNA Vaccination against SARS-CoV-2 Variants: Differing Kinetics and Strong Boosting by Breakthrough Infection.
Introduction: Finally, Delta (B.1.617.2) is responsible for the most recent wave of the COVID-19 pandemic and is characterized by new NTD alterations, together with key RBD mutations (L452R and T478K).
Abstract: In addition to this, SSIPe is used to report the binding affinity between the receptor-binding domain of Spike protein and human ACE2 protein by considering L452R, T478K, E484Q, and N501Y hotspot mutations in that region.
Conclusion: Finally, SSIPe is used to report the binding affinity between the RBD of Spike protein and human ACE2 protein by considering L452R,
Introduction: On the other hand, the variant B.1.617.2 was first identified in India with L452R, T478K, D614G, and P681R mutations in Spike glycoprotein.
Structural analysis of receptor binding domain mutations in SARS-CoV-2 variants of concern that modulate ACE2 and antibody binding.
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.