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 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 D839Y/N/E.
Structural and Functional Analysis of the D614G SARS-CoV-2 Spike Protein Variant.
Method: 3 muL of enriched D614G trimers, at 2.5 mg/mL, was deposited on an UltrAuFoil R1.2/1.3 300 mesh grid that had been glow discharged for 30 s in a GloQube Plus Glow Discharge System.
Method: Analysis of D614G frequency in the public database.
Method: Following the capture of the ACE2.Fc on the anti-human Fc mAb immobilized surface, 0.78 nM - 50 nM, two-fold serial dilutions, in duplicate, of soluble SARS-CoV-2 spike trimer protein, D614 or D614G, were injected for 3 min at a flow rate of 50 mL/min, with a 2 min dissociation phase in the running buffer.
Method: Single-cycle HIV-1 vectors pseudotyped with SARS-CoV-2 Spike protein, either D614 or D614G, were produced by transfection of either HIV-1 pNL4-3 Deltaenv Deltavpr luciferase reporter plasmid (pNL4-3.Luc.R-
Reinfection with SARS-CoV-2 and Failure of Humoral Immunity: a case report.
Abstract: We sequenced viruses from two distinct episodes of symptomatic COVID-19 separated by 144 days in a single patient, to conclusively describe reinfection with a new strain harboring the spik
Result: At day 14 and 42, nAb titers (IC50) were 1:260 and 1:382 against D614 (Wuhan) pseudovirus, and were 1:449 and 1:1168 against a mutated D614G pseudovirus, showing differential increase of nAb to D614G pseudovirus compared to the Wuhan strain (Figures 3D and S5).
Result: Importantly, present in InCoV139-July (but not in InCoV139-March) is the A23403G mutation, which confers the D614G amino acid change in spike protein, and defines the SARS-CoV-2 strain with greater replicative fitness, introduced separately to the US East Coast via Europe.
Chemosensory Dysfunction in COVID-19: Integration of Genetic and Epidemiological Data Points to D614G Spike Protein Variant as a Contributing Factor.
Conclusion: Combined genetic, structural, and epidemiological data suggest that the D614G switch may cause increased prevalence of chemosensory deficits as observed during the pandemic progression from East Asia to Western countries.
Conclusion: The spike protein mutation D614G became dominant in the SARS-CoV-2 virus during the Figure: The D614G substitution, even though it is not located within the RBD (so it will not change the affinity of pure RBD to hACE2), changes the interprotomer spike energetics and enhances RBD exposure, thus favoring the likelihood of binding of the G614-spike protein to hACE2 as compared with the D614 variant.
Variations in SARS-CoV-2 Spike Protein Cell Epitopes and Glycosylation Profiles During Global Transmission Course of COVID-19.
Abstract: The most prominent sequence variation was observed on the spike protein, resulting in the substitution D614G, with a prevalence of 56.2%.
Result: However, the spike protein marker (D614G) varied significantly among viruses, where 28 (43.8%) of the genomes revealed the original aspartic acid residue, which was replaced by glycine in 36 (56.2%) (Table 2).
Table: D614G
Discussion: The most prominent variation is observed on the spike protein marker, resulting in the substitution D614G, with a prevalence of 56.2%.
SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes.
Result: Spike D614G was nearly always co-inherited with Pol P4715L (also radical and altering a perfectly-conserved residue in a highly-conserved context, but potentially-deleterious given Pol's slow evolution and less-likely-to-be-adaptive function), nsp3 nucleotide change C3037T (repeatedly-observed synonymous change, outside synonymously-constrained elements, likely-neutral), and nucleotide change C241T (perfectly-conserved, non-coding, in a loop of six unpaired bases in the conser
Result: Among them, radical-amino-acid-change D614G, which rose in frequency across multiple cities and increases infectivity in vitro, disrupts a perfectly-conserved residue (across Sarbecoviruses), and lies in a stretch of 11 perfectly-conserved amino acids.
SARS-CoV-2 D614G Variant Exhibits Enhanced Replication ex vivo and Earlier Transmission in vivo.
Introduction: After three continuous passages at 72h intervals, the D614G variant became dominant in the cultures regardless of whether the WT virus was at a 1:1 or 10:1 ratio over the isogenic D614G mutant.
Introduction: Although the D614G variant showed similar or slightly higher titers at the early time point (8h), its peak titers were significantly lower than the WT virus in Vero-E6 and A549-ACE2 cell lines but not in Vero-81 and Huh7.
Introduction: Both WT and D614G were transmitted efficiently to naive hamsters evident by positive nasal wash samples detected in all exposed animals at day 4.
Introduction: Consistent with previous studies, we demonstrated the increased sensitivity of the SARS-CoV2 D614G-nLuc variant to the antisera from D-form spike (WT) vaccinat
Non-synonymous mutations of SARS-CoV-2 leads epitope loss and segregates its variants.
Abstract: It is evident that the D614G mutation in spike glycoprotein and P4715L in RdRp is the important determinant of SARS-CoV-2 evolution since its emergence.
Discussion: D614G mutation in spike is the dominant pandemic form that may indicate a fitness advantage and related to severe reduced antigenic specificity.
Discussion: However, careful examination of the cryoEM structure predicts that the interactions with the neighbouring protomer due to D614G mutation is disrupted in absence of negatively charged/hydrogen bond accepting group from the side chain of non-polar glycine.
Discussion: However, it can be anticipated that the replacement of negatively charged Asp into non-polar Gly in D614G<
D614G mutation alters SARS-CoV-2 spike conformational dynamics and protease cleavage susceptibility at the S1/S2 junction.
Abstract: Despite a low mutation rate, isolates with the D614G substitution in the S protein appeared early during the pandemic, and are now the dominant form worldwide.
Abstract: Here, we analyze the D614G mutation in the context of a soluble S ectodomain construct.