Method: Initial screening focused on the N501Y mutation, with screening for both N501Y and E484K initiated in March 2020.
Method: We used Ontario's Case and Contact Management (CCM) database to create a retrospective cohort of SARS-CoV-2 cases who underwent screening for VOCs and had test report dates between 7 February 2021 and 31 October 2021 (as routine screening for N501Y and E484K mutations began on 7 February 2021).
Human serum from SARS-CoV-2-vaccinated and COVID-19 patients shows reduced binding to the RBD of SARS-CoV-2 Omicron variant.
Introduction: Moreover, a B.1.1.7 sub-lineage with an additional E484K substitution in the RBD has been detected in multiple countries.
Introduction: The E484K amino acid change is also found in other VOCs/VOIs and has been shown to reduce antibody neutralization.
Discussion: Interestingly, the VOCs B.1.351 and P.1 escaped LY-COV555 and REGN10933 which was likely facilitated by the E484K mutation present in both variants.
Discussion: This suggests that L452R and E484K lead to an escape from LY-COV555 and to a partial resistance to either REGN10987 or REGN10933, respectively.
Evolution of the SARS-CoV-2 spike protein in the human host.
Method: The following variant spikes were made (SA, Alpha and mink) (all mutations listed with reference to the NCBI sequence YP_009724390.1): 2P Alpha (Delta69-70, Delta144, N501Y, A570D, D614G, P681H, T716A, S982A, D1118H, and K986P, V987P), FUR2P Alpha (Delta69-70, Delta144, N501Y, A570D, D614G, T716A, S982A, D1118H, and R682S, R685S, K
Identifying SARS-CoV-2 Variants of Concern through saliva-based RT-qPCR by targeting recurrent mutation sites.
Method: SARS-CoV-2 TaqMan Assays for S substitutions K417T, E484K, E484Q, and L452R were performed per manufacturer's instructions (Thermo Fisher) with 4 muL of template.
Discussion: The accuracies of K417T, E484K, E484Q, and L452R assays were >= 96.4% (Table 3).
Discussion: We did observe low-level amplification from off-target binding in the E484K, K417T, and L452R assays.
Vaccine-Induced Antibody Responses against SARS-CoV-2 Variants-Of-Concern Six Months after the BNT162b2 COVID-19 mRNA Vaccination.
Result: including N501Y in both Alpha and Beta, E484K in Eta and Beta, K417N in Beta, and L452R and T478K only in Delta.
Discussion: Amino acid changes in spike proteins of variants contribute to immune evasion, and it has been suggested that N501Y is associated with increased infectivity, whereas L452R, T478K, and E484K with K417N reduce the interaction of neutralizing antibodies with RBD.
Discussion: However, Eta with slightly reduced neutralization results has solely an E484K substitution, indicating that the PMID: 35265451
2022
3 Biotech
Introduction: Another variant, B.1.351 (Mwenda et al.) and P.1 variant (Francisco et al.) carries 9 and 11 spike protein mutations, respectively, including 3 mutations in the receptor-binding domain (RBD), K417N/T, E484K, and N501Y.
Characterization of SARS-CoV-2 Variants B.1.617.1 (Kappa), B.1.617.2 (Delta), and B.1.618 by Cell Entry and Immune Evasion.
Introduction: Also, the E484Q mutation is similar to the E484K mutation found in the B.1.351 variant, which exhibited reduced neutralization by convalescent-phase sera or monoclonal antibodies.
Introduction: B.1.618 harbors Delta145-146 (deletion of the 145th and 146th residues) and an E484K mutation in the NTD and RBD, respectively.
Introduction: For the Kappa and Delta variants, this is the first time that L452R and E484Q (Kappa)/T478K (Delta) mutations have been found to coexist and the first time that P681R has been observed; for B.1.618, this is the first time the combination of Delta145-146 in the NTD domain and E484K has been observed.
Introduction: In
Evolutionary history of the SARS-CoV-2 Gamma variant of concern (P.1): a perfect storm.
PMID: 35266951
2022
Genetics and molecular biology
Introduction: Currently, the WHO has identified the Gamma lineage (B.1.1.28.1, P.1 or Gamma; Nextstrain clade 20J/V3) with the following key S mutations: L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I, and V1176F.
Introduction: The WHO and other reports identified several key SARS-CoV-2
Result: Notably, in our analysis, a number of these sites (e.g., E484K) did not exhibit evidence of positive selection.
Table: E484K
A Bifluorescent-Based Assay for the Identification of Neutralizing Antibodies against SARS-CoV-2 Variants of Concern In Vitro and In Vivo.
Abstract: Here, we report the generation and use of a recombinant (r)SARS-CoV-2 USA/WA1/2020 (WA-1) strain expressing Venus and an rSARS-CoV-2 strain expressing mCherry and containing mutations K417N, E484K, and N501Y found in the receptor binding domain (RBD) of the spike (S) glycoprotein of the South African (SA) B.1.351 (beta [beta]) VoC in bifluorescent-based assays to rapidly and accurately identify human monoclonal antibodies (hMAbs) able to neutralize both viral infections in vitro and in vivo.
Introduction: Using this strategy, we have successfully rescued Venus-and mCherry-expressing rSARS-CoV-2 USA/WA1/2020 (WA-1) and a new rSARS-CoV-2 strain expressing mCherry and containing mutations K417N,