Introduction: Among the SARS-CoV-2 variants of concern, Beta B.1.351 (RBD-K417N/E484K/N501Y) discovered in South Africa and Gamma P.1 (RBD
Discussion: Our comprehensive escape mutation map based on the natural substitutions of the binding hot spots not only confirms the widely circulating strains carrying important immune escape RBD mutations such as K417N, E484K, and L452R, but also facilitates the identification of new immune escape-enabling mutations that are already present at clinical isolates such as F486L, N450K, F490S, and R346S.
A monoclonal antibody that neutralizes SARS-CoV-2 variants, SARS-CoV, and other sarbecoviruses.
Introduction: As an example, a single mutation, E484K, found in several variants could knock out a class of antibodies binding the receptor binding motif (RBM) on the viral spike.
Result: Here we assessed 2-36 activity on more variants, including pseudoviruses representing the combination of key spike mutations of B.1.427/B.1.429, R.1, B.1.1.1, B.1.525, B.1.617.1, B.1.617.2 and B.1.1.7 with E484K, as well as many pseudoviruses with single spike mutations which are naturally circulating in COVID-19 patients with high frequency and located in the N-terminal domain, RBD, or S2.
The evaluation of potential global impact of the N501Y mutation in SARS-COV-2 positive patients.
Introduction: On the other hand, in B.1.351 lineage, the K417N, and E484K mutations are found in the RBD region.
Result: Sequence alignment of RBD from SARS-CoV-2, B.1.1.7, and B.1.351 variants spike proteins are (the N501Y, K417N, and E484K mutations) shown in red with circle.
Discussion: Moreover, SARS-Cov-2 variants include the two Alpha variants (B.1.1.7, United Kingdom and B.1.1.7 with the additional E484K mutation), the Beta variant (B.1.351, South Africa), and the Gamma variant (P.1, Brazil).
Rapid Automated Screening for SARS-CoV-2 B.1.617 Lineage Variants (Delta/Kappa) through a Versatile Toolset of qPCR-Based SNP Detection.
Method: Based on previous works, for detecting del-HV69/70 and N501Y via RT-qPCR, we designed and tested further assays to be
Result: As part of this study, the following RT-PCR assays were evaluated for technical viability: E484K/Q, P681H/R, L452R, V1176F, del-Y144/145.
Result: The only assay showing significant off-target activity was E484-WT with the E484K sequence, which was eliminated by setting an end-point fluorescence cut-off.
Discussion: For example, the recently emerged B.1.617 (first detected in India) lineages feature E484Q (only B.1.617.1/3) and P681R SNPs instead of the more common E484K and P681H.
In Vitro Effect of Taraxacum officinale Leaf Aqueous Extract on the Interaction between ACE2 Cell Surface Receptor and SARS-CoV-2 Spike Protein D614 and Four Mutants.
Abstract: This could be shown for the wild type and mutant forms (D614G, N501Y, and a mix of K417N, E484K, and N501Y) in human HEK293-hACE2 kidney and A549-hACE2-TMPRSS2 lung cells.
Method: Then, 500 ng/mL SARS-CoV-2 Spike S1 (Trenzyme GmbH, Konstanz, Germany), spike S1 D614G, N50Y, or a mix of K417N, E484K, and N501Y (Sino Biological Europe GmbH, Eschborn, Germany)-His recombinant protein were added into each sample, and samples were further incubated for 30-60 min.
Result: Also, in this setting, a mixture of spike mutants
Evidence for retained spike-binding and neutralizing activity against emerging SARS-CoV-2 variants in serum of COVID-19 mRNA vaccine recipients.
Introduction: Here, we tested the neutralizing activity of a panel of 30 post-mRNA SARS-CoV-2 vaccination sera against the seven emerging variants (three Iota sub-lineages, Alpha-E484K, Beta, Delta and a Lambda sub-variant) using a microneutralization assay designed to allow for multi-cycle replication with sera/antibodies being present in the overlay at all times to better mimic physiological conditions.
Introduction: In comparison with the WA-1 wild type reference virus, we found that differences in neutralization activity were minimal for Delta and the three Iota sublineages with a greater reduction being observed for the Beta and Alpha (E484K) variants as well as for a Lambda subvariant.
Introduction: These include Iota (B.1.526) which emerged in New York City and comprises three different sub-lineages, Epsilon (B.1.427/B.1.429) which emerged in California, Lambda (C.37) which emerged in Peru (preprint), Delta (
Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant-dependent manner.
Method: SARS-CoV-2 pseudotyped lentiviruses were prepared by co-transfecting the HEK293T cell line with either the SARS-CoV-2 ancestral variant spike (D614G), the Beta spike (L18F, D80A, D215G, K417N, E484K, N501Y, D614G, A701V, 242-244 del) or the Delta spike (T19R, R158G L452R, T478K, D614G, P681R, Table: E484K
Emerging SARS-CoV-2 variants expand species tropism to murines.
Result: 1e-g), suggesting the K417N/T and E484K mutation in the RBD of these variants might further facilitate mouse adaptation in addition to the N501Y substitution.
Discussion: Apart from the N501Y mutation, several amino acid substitutions including K417N, E484K, Q493H/K, and Q498H were also suggested to be critical for SARS-CoV-2 adaptation in murine species.
Discussion: This is congruous with our observation that B.1.351 replicated to a higher level than B.1.1.7 and P.3 in wildtype mice since B.1.351 carries K417N, E484K in addition to N501Y.
Functional Effects of Receptor-Binding Domain Mutations of SARS-CoV-2 B.1.351 and P.1 Variants.
Result: At the same time, the E484K and N501Y RBD still caused a significant decrease in the median inhibitory potency of fully vaccinated sera (1.7-fold and 1.3-fold decrease respectively) (p < 0.0001 for both).
Result: Both the E484K and N501Y alone and as part of the N_K_Y and T_K_Y significantly impaired the antibody-mediated inhibition (p < 0.0001 for all), ranging from a 1.5-fold decrease for the N501Y alone, to a 2.39-fold for the combined T_K_Y (medians 51.33 wt, 32.26 E484K, 34.2 N501Y, 23.71 N_K_Y, 21.45 T_K_Y).
Result: The E484K and N501Y Mutations Enhance the Evasion Capacity of B.1.351 and P.1 Against Natural-Induc
Global Prevalence of Adaptive and Prolonged Infections' Mutations in the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein.
Abstract: Irrespective of the geographical region, in the case of the adaptive mutations, N501Y (48.38%) was found to be the dominant mutation followed by L452R (17.52%), T478K (14.31%), E484K (4.69%), S477N (3.29%), K417T (1.64%), N439K (0.7%) and S494P (0.7%).
Method: Some adaptive mutations, namely Y453F, S477N, T478K, E484K, S494P and N501Y, were also found in long-term COVID-19 infections.