Abstract: Further examination revealed that this interaction between the virus and human T cells is strengthened in the context of a recently reported rare mutation (D839Y/N/E) from a European strain of SARS-CoV-2.
Method: Two mutants associated with European Covid-19 patients were constructed using CHARMM-GUI: one is the main strain mutant D614G and the other contains four mutations including Q239K, A831V, D614G and D839Y.
Result: Interestingly, the SARS-CoV-2 s
Result: Thus, the D839Y/N/E mutations would be expected to strengthen/support the above described association between the superantigenic PRRA-containing segment and the TCRVbeta.
An engineered decoy receptor for SARS-CoV-2 broadly binds protein S sequence variants.
Method: To explore the frequency of Spike D839Y variant at worldwide level, we downloaded all the amino acid sequences (and associated metadata) of SARS-CoV-2 spike protein available at GISAID (as of 23 July 2020).
Discussion: Besides the potential functional role of D839Y mutation and its high prevalence in Portugal, its detection in 12 other countries from four continents, it's probable independent emergence in distinct times and genetic clades (20A and 20C) in some of these countries and its considerable relative weight (~5%) in the sampled
Discussion: In another perspective, one cannot rule out that the high dissemination could have also been driven by fitness increase mediated by the D839Y mutation, which would be consistent with its estimated frequency increase from 13.3% to 33.1% in a 4-week period.
SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes.
Result: Another three are in moderately-conserved contexts (V367F, D839Y/N/E, D936Y/H) less likely to be functional, and eight lie in repeatedly-altered amino acids in poorly-conserved regions and likely-neutral.
Variations in SARS-CoV-2 Spike Protein Cell Epitopes and Glycosylation Profiles During Global Transmission Course of COVID-19.
Result: Binding level results of T29I, V367F, A706V, and A831V demonstrated that these substitutions had low binding affinity in HLA-A01:01, HLA-B07:02, and HLA-B35:01 compared to the wild type, while H49Y, Q239K, V483A, D839Y, S943P, A1078S, and P1263L substitutions still had strong binding affinity with HLA molecules.
Result: For variant S proteins, T29I, H49Y, Q239K, V367F,
Table: D839Y
Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation.
Abstract: This interaction between the virus and human T cells could be strengthened by a rare mutation (D839Y/N/E) from a European strain of SARS-CoV-2.
Conclusion: We show that the mutation D839Y found in a European strain of SARS-CoV-2 enhances the binding affinity of the SAg motif to the TCR.
Result: Interestingly, the SARS-CoV-2 S binding region harbors three residues that have been recently reported to have mutated in new strains from Europe and the United States: D614G, A831V, and D83
Result: The interfacial interactions in the D839Y mutant are stabilized by a hydrogen bond between Y839 and D32, an aromatic (polar-pi) interaction between Y839 and N30, and possible electrostatic interactions with K73 and S97.
The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity.
Result: First, we investigated Sarbecovirus conservation of 14 amino acids in the spike protein in which mutations appear to be accumulating in the SARS-CoV-2 population, namely D614G, L5F, L8V/W, H49Y, Y145H, Q239K, V367F, G476S, V483A, V615I/F, A831V, D839Y/N/E, S943P, P1263L.