SARS-CoV-2 Variants, RBD Mutations, Binding Affinity, and Antibody Escape.
PMID: 34829998
2021
International journal of molecular sciences
Abstract: The variant-induced risk of breakthrough infections in vaccinated people is attributed to the L452R mutation's reduction of the binding affinity of many antibodies.
Conclusion: Variant-induced risk of breakthrough infections among vaccinated people was attributed to the L452R mutations, decreasing the binding affinity of many antibodies.
Introduction: Surprisingly, the mutations of L452R, K417N,
Discussion: However, the change from Leucine (L) to arginine (R) at the amino-acid position 452 due to the mutation L452R introduces two hydrogen bond (i.e., the ADD) interactions between E35 and R452 (see Figure 2d,e).
Discussion: The mutation L452R thus increases the binding affinity between the RBD and the ACE2.
Curcumin Inhibits In Vitro SARS-CoV-2 Infection In Vero E6 Cells through Multiple Antiviral Mechanisms.
Discussion: Taking into account that curcumin exhibited inhibition against D614G strain, through different treatment strategies, this compound was evaluated against infection by the Delta variant which contains mutations in the spike protein (L452R, T478K, P681R, and D614G) associated with an increase in viral infectivity, transmissibility and pathogenicity in individuals infected with SARS-CoV-2 and a decrease in antibody-mediated neutralization.
High Individual Heterogeneity of Neutralizing Activities against the Original Strain and Nine Different Variants of SARS-CoV-2.
Result: In the case of the Marseille-501/A.27 variant, the L452R mutation is associated with N501Y.
Result: The L452R substitution is present in both the Marseille-501/A.27 (Figure 4C) and the Delta (Figure 4D) variants, yet in a distinct mutational context.
Result: The case of the Delta variant is more puzzling, since, in this case, the substitution L452R is associated with T478K instead of N501Y.
Discussion: Due to its key spike protein mutations (L452R and T478K), the Delta variant may induce an immune evasion, similar to the B.1.351.2, P.1, and R.1 variants.
Impact of the Double Mutants on Spike Protein of SARS-CoV-2 B.1.617 Lineage on the Human ACE2 Receptor Binding: A Structural Insight.
Result: The delta variant, which carried L452R and T478K mutations, also demonstrated a reduced affinity towards the LY-CoV555.
Result: The occurrence of L452R and E484Q mutations in the kappa variant severely impacted the affinity of LY-CoV555.
Result: The reference complex structures along with the kappa (L452R, E484Q) and delta variant (L452R and T478K) models were subjected to two hundred nanoseconds of MD simulations.
Discussion: The dual mutations (L452R + E484Q and L452R + T478K) harbored by the novel variants (kappa and delta) were found to be re
Codon usage, phylogeny and binding energy estimation predict the evolution of SARS-CoV-2.
PMID: 34841034
2021
One health (Amsterdam, Netherlands)
Introduction: As reported by an in vitro neutralizing assay performed with pseudo-typed viruses, L452R increases resistance to some monoclonal antibodies, while in-field observations suggest that administering one dose of the BNT162b2 vaccine produces 5.8 times lower neutralizing activity for variant B.1.617.2 (delta) than for variant B.1.1.7 (alpha).
Introduction: This variant does not have the amino acid substitution N501Y but exhibits two other substitutions: L452R and T478K.
Phylogenomics and population genomics of SARS-CoV-2 in Mexico during the pre-vaccination stage reveals variants of interest B.1.1.28.4 and B.1.1.222 or B.1.1.519 and the nucleocapsid mutation S194L associated with symptoms.
Introduction: Shortly after the appearance of D614G, other mutations in the Receptor Binding Domain (RBD) of the spike protein appeared, including but not limited to K417N, L452R, E484K and N501Y.
Result: With only 25 sequences available, this analysis also identified covariances between S13I, L452R and W152C of the VOI B.1.427/9.
Molecular insights into receptor binding energetics and neutralization of SARS-CoV-2 variants.
Differential Interactions between Human ACE2 and Spike RBD of SARS-CoV-2 Variants of Concern.
PMID: 34856802
2021
Journal of chemical theory and computation
Abstract: Among all variants investigated in this work, RBD of the Epsilon (L452R) variant is relatively easily detached from ACE2.
Abstract: We report that RBD of the Alpha (
Method: From the WT RBD structure, each variant was modeled with the following mutations: Alpha (N501Y), Beta (K417N, E484K, N501Y), Gamma (K417T, E484K, N501Y), Epsilon (L452R), Kappa (L452R, E484Q), and Delta (L452R, T478K).
Recognition of Variants of Concern by Antibodies and T Cells Induced by a SARS-CoV-2 Inactivated Vaccine.
Discussion: Here we show using a RBD containing the mutations T478K and L452R present in the Delta variant that volunteers vaccinated with CoronaVac exhibit reduced blocking antibodies compared to the WT RBD but we report a seropositivity of 78.57% and 55.76% by sVNT and cVNT ( Tables 1 and 2 ), respectively, which suggests that the vaccine confers protection against this variant.
Discussion: Pseudoviruses carrying the L452R mutation display higher infectivity in cell culture and when incubated with sera from subjects vaccinated with Moderna mRNA-1273 or BNT16b2, as compared to the WT strain.
Discussion: The Delta variant (first identified in India) exhibit the RBD mutations T478K, L452R and
Evolutionary and Antigenic Profiling of the Tendentious D614G Mutation of SARS-CoV-2 in Gujarat, India.
Abstract: The D614G variant in spike protein is reported to have a very high frequency of >95% globally followed by the L452R and P681R, thus getting significant attention.
Discussion: In addition, it is concurrently seen with other mutations like P681R, L452R, T19R, E156G, T478K.
SARS_CoV_2 mutation literature information.
PMID: 
2021
International journal of molecular sciences
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