Allosteric Determinants of the SARS-CoV-2 Spike Protein Binding with Nanobodies: Examining Mechanisms of Mutational Escape and Sensitivity of the Omicron Variant.
PMID: 35216287
2022
International journal of molecular sciences
Introduction: Neutralization of SARS-CoV-2 by low-picomolar and mutation-tolerant VHH nanobodies that bind synergistically to the opposite sides of the RBD produced a binding avidity effect unaffected by immune-escape mutants K417N/T, E484K, N501Y, and L452R.
Rapid detection of the widely circulating B.1.617.2 (Delta) SARS-CoV-2 variant.
Abstract: Whole genome sequencing of 46 randomly selected samples validated the strains identified as positive and negative for the B.1.617.2 (Delta) variant and confirmed the S gene deletion in addition to B.1.617.2 characteristic mutations including L452R, T478K, P681R and D950N located in the
Introduction: L452R is known to increase affinity for ACE2 receptors found on the surface of a variety of human cells such as lung cells, while the T478K has been shown to increase receptor binding activity and to enable immune escape.
Introduction: In addition, it shows multiple mutations including L452R, T478K, and D950N.
A Detailed Overview of Immune Escape, Antibody Escape, Partial Vaccine Escape of SARS-CoV-2 and Their Emerging Variants With Escape Mutations.
Abstract: Simultaneously we have discussed the significant mutations related to emerging variants and immune escape, such as mutations in the RBD region (N439K, L452R, E484K, N501Y, K444R) and other parts (D614G, P681R) of the S-glycoprotein.
Introduction: 4.1.3.2 L452R.
Introduction: Another significant mutation noted in the RBD region is L452R.
Introduction: Few mutations include K417T/N, E484K,
Table: L452R
Molecular and Epidemiological Characterization of Emerging Immune-Escape Variants of SARS-CoV-2.
Method: For instance, a Delta variant spike haplotype consisting of T19R, 256_258delinsG, L452R, T478K, D614G, P681R, and D950N is also assigned to another haplotype group of T19R, L452R, T478K, D614G, P681R, and D950N, which is missing a 256_258delinsG variant.
SARS-CoV-2 Beta and Delta variants trigger Fc effector function with increased cross-reactivity.
Method: The SARS-CoV-2 Wuhan-1 spike, cloned into pCDNA3.1 was mutated using the QuikChange Lightning Site-Directed Mutagenesis kit (Agilent Technologies) and NEBuilder HiFi DNA Assembly Master Mix (NEB) to include D614G (original) or lineage defining mutations for Alpha (DEL69-70, DEL144, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H), Beta (L18F, D80A, D215G, 242-244del, K417N, E484K, N501Y, D614G and A701V<
Human serum from SARS-CoV-2-vaccinated and COVID-19 patients shows reduced binding to the RBD of SARS-CoV-2 Omicron variant.
Result: L18F is present in the VOCs B.1.351 and P.1, the L452R substitution is found in high frequencies in B.1.617.2 and related AY lineages, and N501Y is known from B.1.1.7, B.1.351 and P.1.
Result: Both regions are targets for neutralizing antibodies and L18F and L452R have been previously associated with antibody escape and L452R additionally with increased infectivity.
Result: Lineage A.27 has two mutations in its RBD that translate to L452R and N501Y.
Result: The L18F amino acid substitution is found within the first of five loops of the NTD supersite and the
Table: L452R
Identifying SARS-CoV-2 Variants of Concern through saliva-based RT-qPCR by targeting recurrent mutation sites.
Introduction: Additionally, L452R increases both structural stability and viral fusogenicity, and decreases cell-mediated immune response.
Introduction: Conveniently, the currently circulating Omicron variant (B.1.1.529) harbors both L452R and SDelta69-70, so we used these assays to quickly identify its emergence at Clemson University and the surrounding Upstate South Carolina in December 2021.
Introduction: We also evaluated the efficacy of TaqPath assays for K417T, E484K, E484Q, and L452R in saliva.
Introduction: We chose to evaluate assays for biochemically significant mutations that also provide differential strain typing for SARS-CoV-2 VOCs, namely SDelta69-70, ORF1aDelta3675-3677, K417T, E484K
Systemic effects of missense mutations on SARS-CoV-2 spike glycoprotein stability and receptor-binding affinity.
Result: We observed that G476S can decrease RBD-ACE2 binding affinity (DeltaDeltaDeltaG = 0.751 kcal/mol), but L452R has small stabilizing effect (DeltaDeltaDeltaG = -0.395 kcal/mol) on RBD-ACE2 complex.
Discussion: Notably, the presence of the A475V, L452R, V483A, and F490L mutations in the RBD domain of SARS-CoV-2 was shown to decrease the neutralizing activity of antibody and might impede the development of therapeutic antibodies (Li et al, 2020).
SARS_CoV_2 mutation literature information.
PMID: 
2022
International journal of molecular sciences
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