Evaluation of the clinical and analytical performance of the Seegene allplex SARS-CoV-2 variants I assay for the detection of variants of concern (VOC) and variants of interests (VOI).
Introduction: With ten different mutations in the S gene including L452R and D614G this variant showed an increased transmissibility and vaccine effectiveness is also reduced.
Table: L452R
SARS-CoV-2 monoclonal antibodies with therapeutic potential: Broad neutralizing activity and No evidence of antibody-dependent enhancement.
Figure: (a) Binding responses of anti-SARS-CoV-2 S protein mAbs, S1D2-hIgG1, STI-1499-LALA and 1741-LALA to the S1 fragment of the S protein from SARS-CoV-2 variants, including 2019-nCoV, B.1.1.7 (HV69-70 deletion, Y144 deletion, N501Y, A570D, D614G, P681H)-, B.1.351 (K417N, E484K, N501Y, D614G)-, and B.1.617.2 (T19R, G142D, E156G, 157-158 deletion, L452R, T478K, D614G, P681R)- lineage.
SARS-CoV-2 Virus-Host Interaction: Currently Available Structures and Implications of Variant Emergence on Infectivity and Immune Response.
PMID: 34639178
2021
International journal of molecular sciences
Discussion: L452R has also appeared in variant Epsilon identified in California, reaching a maximum of 20% of new cases in the United States, before variant Delta became prevalent.
Discussion: Mutation L452R causes a steric hindrance to Ab binding, retrieved from structure 7CM4, without affecting binding to hACE2 (Figure 10) but causing a greater than 10-fold decrease in neutralization potency for RBD-specific Abs.
Discussion: Potentially fundamental for immune escape are mutations K417N, and particularly L452R, both affecting Ab binding, and occurring in the RBD.
Molecular rationale for SARS-CoV-2 spike circulating mutations able to escape bamlanivimab and etesevimab monoclonal antibodies.
Discussion: However, L452R is a spike mutation of interest (MOI) present in the VOC lineages B.1.427/B.1.429 (reported in California, USA, on 09/20, now Epsilon), B.1.526.1 (New York City, USA, 10/20, Iota subtype), and in the B1.617.1 (Kappa)/B.1.617.2 (Delta)/B.1.617.3 lineages now rapidly and deadly spreading in India (12/20-02/21), where it is always found along with the D614G substitution.
Discussion: Importantly, the L452R mutation is also present in tandem with E484Q, in particular in the B.1.617.1 (Kappa) variant that is responsible for actual disease outbreaks in 49 countries in all six WHO regions.
Discussion: Our present data support the escaping potential of the L452R viral mutation with respect to bamlanivimab.
Discussion: Using a pseudo-virus expressing
The evolution of the mechanisms of SARS-CoV-2 evolution revealing vaccine-resistant mutations in Europe and America.
3Introduction: Moreover, we have pointed out that Y449S and Y449H are two vaccine-resistant mutations, and ""Y449S, S494P, K417N,
Introduction: Later on, we have provided a list of most likely vaccine escape RBD mutations with high frequency, including S494P, Q493L, K417N, F490S, F486L, R403K, E484K, L452R, K417T, F490L, E484Q, and A475S.
Genomic surveillance of SARS-CoV-2 tracks early interstate transmission of P.1 lineage and diversification within P.2 clade in Brazil.
Result: We found 16 SNVs targeting the receptor-binding domain (RBD) in S1, of which eight were missense variants, including K417T, N439K, L452R, S477R, E484K, N501Y, L518I, A522V.
Ten emerging SARS-CoV-2 spike variants exhibit variable infectivity, animal tropism, and antibody neutralization.
Result: Furthermore, the variant B.1.429 and L452R single-mutation strain showed reduced susceptibility to mAbs 9G11 and X593; the variant B.1.526-1(S477N) and S477N single-mutation strain showed reduced susceptibility to mAb 7B8, and variant B.1.1.298 and Y453F single-mutation strain showed reduced sensitivity to mAb 1F9.
Result: However, the immune escape of 9G11 caused by L452R and E484K cannot be directly explained by salt bridge destruction or hydrogen bond changes.
Result: The L452R single mutation and B.1.526-2 led to increased infectivity, whereas the B.1.1.298 variant exhibited significantly decreased infectivity in all the four cell lines.
Figure: b Structural modelling of the K417N/T
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
Abstract: The newly emerging Kappa, Delta, and Lambda SARS-CoV-2 variants are worrisome, characterized with the double mutations E484Q/L452R, T478K/L452R, and F490S/L452Q, respectively, in their receptor binding domains (RBDs) of the spike proteins.
Abstract: To verify simulation results, we further carried out experiments with both pseudovirions- and live virus-based neutralization assays and demonstrated that LY-CoV555 completely lost neutralizing activity against the L452R/E484Q mutant.
Abstract: Using all-atom molecular dynamics (MD) simulation, here, we show that the PMID: 34648735
2021
Cell reports
Table: L452R
Figure: (A and B) In vitro infection assay of VSV PsVs, including N501Y + D614G, N501Y + L452R + D614G, and N501Y + K417N +
Discussion: There are many potential explanations for the lower infectivity observed for the Los Angeles variant, including the theory that L452R drives enhanced transmissibility but not necessarily infectivity.
Discussion: This is further supported by our study regarding infectivity of PsVs incorporating mutations found in the India variant because the L452R mutation was also present and did not mediate enhancement of infection compared with the South Africa variant PsV.
Genomic reconstruction of the SARS-CoV-2 epidemic in England.
Introduction: In contrast to other VOCs, Delta/Kappa do not contain N501Y or E484K mutations, but their L452R mutation may reduce antibody recognition and P681R enhances furin cleavage, similar to the P681H mutation of Alpha.
SARS_CoV_2 mutation literature information.
PMID: 
2021
Journal of clinical virology
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