Modeling SARS-CoV-2 spike/ACE2 protein-protein interactions for predicting the binding affinity of new spike variants for ACE2, and novel ACE2 structurally related human protein targets, for COVID-19 handling in the 3PM context.
Abstract: By using our pipeline, we built 3D comparative models of the SARS-CoV-2 spike RBD/ACE2 protein complexes for the VoC B.1.1.7-United Kingdom (carrying the mutations of concern/interest N501Y, S494P, E484K at the RBD), P.1-Japan/Brazil (RBD mutations: K417T, E484K, N501Y), B.1.351-South Africa (RBD mutations: K417N, E484K, N501Y), B.1.427/B.1.429-California (RBD mutations: L452R), the B.1.141 (
Predominance of antibody-resistant SARS-CoV-2 variants in vaccine breakthrough cases from the San Francisco Bay Area, California.
Abstract: Vaccine breakthrough infections were more commonly associated with circulating antibody-resistant variants carrying >=1 mutation associated with decreased antibody neutralization (L452R/Q, E484K/Q and/or F490S) than infections in unvaccinated individuals (78% versus 48%, P = 1.96 x 10-8).
Analysis of SARS-COV2 spike protein variants among Iraqi isolates.
Introduction: This variant is characterized by having several mutations in the spike proteins including L452R, T478K and P681R.
Result: Previously, the L452R variant was shown to become resistant to monoclonal antibodies (mAbs) X593 and P2B-2F6, however, mutating leucine (L) to glutamine (Q) or methionine (M) among the Iraqi strains could affect differently on the sensitivity of the strain towards the host and/or vaccine-induced immunity.
Emergence of two distinct variants of SARS-CoV-2 and an explosive second wave of COVID-19: the experience of a tertiary care hospital in Pune, India.
Abstract: Concurrent with the upsurge of the second wave in March 2021, 73% (33/45) of RBD sequences harboured L452R/E484Q mutations characteristic of the Kappa variant.
Abstract: In April 2021, co-circulation of Kappa (37%) and Delta (L452R/T478K, 59%) variants was recorded.
Result: All six Indian variants of the B.1.617.1
Discussion: Interestingly, the L452R mutation was maintained.
Discussion: Regarding the L452R and E484Q mutations in the Kappa variant, the substitution of a hydrophobic leucine (L) with a hydrophilic arginine (R) is similar to what occurred in the California variant, which was shown to correlate with increased transmissibility and decreased antibody neutralization.
A CLUSTER OF SARS-COV-2 DELTA VARIANT OF CONCERN ADDITIONALLY HARBORING F490S, NORTHERN LOMBARDY, ITALY.
PMID: 34995777
2022
International journal of infectious diseases
Introduction: T478K and L452R are the main mutations of concern (MOC) within the Spike protein of Delta.
A bivalent nanoparticle vaccine exhibits potent cross-protection against the variants of SARS-CoV-2.
Introduction: Given that the B.1.351 and P.1 strains harbor K417N/T, E484K, and N501Y mutations in the RBD domain, B.1.526 harbors E484K, and B.1.617.1 harbors L452R and E484Q (Figure S4C), we wanted to develop a D614G- and E484K/Q-specific bivalent vaccine.
Introduction: Some recent studies also show that the protection efficiency of these vaccines against other variants harboring E484K/Q mutations, such as B1.617.1 harboring L452R/E484Q, is decreased.
Engineered small extracellular vesicles displaying ACE2 variants on the surface protect against SARS-CoV-2 infection.
PMID: 34982509
2022
Journal of extracellular vesicles
Abstract: Furthermore, engineered sEVs inhibit the entry of wild-type (WT), the globally dominant D614G
Result: To test whether S mutations confer resistance against sACE2-loaded sEVs, we generated SARS-CoV-2 pseudovirus containing D614G mutant, RBD mutations in Beta variant-K417N, E484K, and N501Y, and mutations in Delta variant L452R, E484K, and D614G (Figure S3a, Supporting Information).
Figure: (g,h) Infectivity of pseudovirus bearing Delta variant S (L452R, E484K, D614G) proteins (n = 4).
Computational modelling of potentially emerging SARS-CoV-2 spike protein RBDs mutations with higher binding affinity towards ACE2: A structural modelling study.
PMID: 34979405
2022
Computers in biology and medicine
Result: Among the reported mutations, N501Y, E484K, K417 N, E484Q and L452R elevate the pathogenicity scale.
A low-cost TaqMan minor groove binder probe-based one-step RT-qPCR assay for rapid identification of N501Y variants of SARS-CoV-2.
PMID: 34656702
2022
Journal of virological methods
Introduction: Our laboratory is developing another TaqMan MGB probe-based one-step RT-qPCR assay to detect the presence of L452R mutation, which shall be used in conjunction with N501Y RT-qPCR.
Introduction: The major limitation of the assay is its inability to detect the recently expanding SARS-CoV-2 variant of concern, B.1.617.2 lineage, (a.k.a G/452R.V3), which does not harbour N501Y mutation but E484Q and L452R instead.
The SARS-CoV-2 Lambda variant exhibits enhanced infectivity and immune resistance.
Figure: HLA-A24+ CTL lines established from 6 BNT162b2-vaccinated donors were stimulated with 1 nM NF9 peptide or its derivatives, NF9-
Discussion: A common feature of the Lambda, Delta, and Epsilon variants is a substitution in L452 of the SARS-CoV-2 S protein: the Lambda variant harbors the L452Q mutation, while the Delta and Epsilon variants possess the L452R mutation.
Discussion: These are reminiscent of our recent study showing that the L452R mutation confers similar virological phenotypes.
Discussion: Together with our previous observation that the L452R mutation enhances viral infectivity, these results strongly suggest that the relatively higher infectivity of the Lambda, Delta, and Epsilon variants is attributed to the L452Q/R mutation.
SARS_CoV_2 mutation literature information.
PMID: 
2022
The EPMA journal
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