Result: Interesting, replacing the viral spike E484 with each of the alternative residues consid
Discussion: 2A,B, Table S2), we considered all possible mutations actually reported at this position in circulating viral variants (i.e., E484A/D/G/K/Q/R/V), and found that all these amino acid variations should confer strong escaping ability to bamlanivimab.
Discussion: Spike variants identified in these studies that presented reduced susceptibility to the LY-CoV555 mAb included the following substitutions: E484D/K/Q, F490S, Q493R, and S494P.
Discussion: Moreover, the E484Q/V/A/G/D mutations have been just described by Chen et al.
Characterization of SARS-CoV-2 East Java isolate, Indonesia.
Discussion: Thus, the analysis of the SARS-CoV-2 spike gene shows the mutation of D614G that increases SARS-CoV-2 infectivity, whereas the E484D mutation was correlated with human immune serum neutralization resistance.
Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization.
Result: Several mutants required higher (3-5-fold) concentrations of hACE2 to block infection, including substitutions at T345A, T345N,
Result: To extend these findings, we employed a higher throughput screening assay to test 16 additional human sera (11, 15, 16, 18, 21, 23, 27, 28, 30, 31, 32, 34, 35, 37, 38, and 39) for their ability to neutralize the VSV-SARS-CoV-2 mutants N450Y, S477N, E484A, E484D, and E484K (Figure 4D).
Discussion: Four variants at this position (E484A, E484D, E484G, and E484K) exhibited resistance to each of the human convalescent sera we tested.
Mutations of SARS-CoV-2 RBD May Alter Its Molecular Structure to Improve Its Infection Efficiency.
Discussion: For instance, N439K, L452R, T478I, and E484D mutations on RBM have significant free energy changes, and they constitute approximately 58% of all mutations on RBD.
In vitro selection of Remdesivir resistance suggests evolutionary predictability of SARS-CoV-2.
Result: Importantly, in our in vitro passaged viruses we observed both synonymous and non-synonymous substitutions occurring at the same sites within spike (H69R, E484D, N501T, H655Y, P681P) as those identified in the emerging SARS-CoV-2 variants of concern (Alpha (B.1.1.7): Delta69/70, N501Y, Result: Of note are the four spike substitutions which occurred within the receptor binding domain (RBD) at either consensus (E484D, & N501T) or sub-consensus (G413R & Q498H) frequency.
Trajectory of Growth of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants in Houston, Texas, January through May 2021, Based on 12,476 Genome Sequences.
PMID: 34303698
2021
The American journal of pathology
Result: Of note, 11 patients infected with B.1.1.7 plus the E484K amino acid change, and one patient each infected with B.1.1.7 sample plus either an E484Q or an E484D amino acid change were identified.
Result: Three hundred and sixty-three samples were identified with changes at E484 (E484K, n = 353; E484Q, n = 9; and E484D, n = 1) that occurred in many genetically diverse SARS-CoV-2 lineages were identified, some of which have not shared a recent common ancestor.
Simultaneous evaluation of antibodies that inhibit SARS-CoV-2 variants via multiplex assay.
Result: Confirming multiplex ACE2 EC50 assay observations, variants E484K and E484D demonstrated reduced affinity to ACE2 (KD 37.2 nM and KD 110.8 nM, respectively).
Result: In addition, 1 variant that showed a reduced affinity for ACE2 (E484D) was selected to be profiled for comparison.
Result: Variants with mutations at positions 446 and 484 (with the exception of E484D) of the RBD prominently demonstrated antibody escape and consequently poor inhibition.
Discussion: Specifically, within the mAb panel, we found variants at positions 446 and 484 (with the exception of E484D) were poorly neutralized.
Systematic analysis of SARS-CoV-2 infection of an ACE2-negative human airway cell.
Result: Moreover, the E484D mutation within the RBD of S is required in H522 cells, but not ACE2-expressing cells.
Result: The E484D S variant has been found to circulate within the human population, and given the alternative mechanism of entry and the requirement for the E484D substitution, we evaluated the ability of sera from vaccinated and convalescent individuals to block the infection of H522 cells.
Result: This revealed the presence of the E484D substitution within the RBD and the less prevalent R682W substitution within the furin cleavage site.
Discussion: This study does not establish why the E484D variant enab
Recent progress on the mutations of SARS-CoV-2 spike protein and suggestions for prevention and controlling of the pandemic.
PMID: 34146731
2021
Infection, genetics and evolution
Introduction: Moreover, to date, four mutations have been identified in amino acid 484 of spike protein, namely E484A, E484G, E484D, and E484K, and each mutation has partial resistance to the convalescent plasma, indicating that amino acid 484 is also one of the dominant epitopes of spike protein.