- Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus.
(Kim et al. (2021))
Tissue specific neutralization
- The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract.
(Planas et al. (2021))
- ~4x more efficient S2 domain cleavage compared to wild type in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3).
(Kim et al. (2021))
- No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3.
(Kim et al. (2021))
- Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry) (Barrett et al. (2021))
- We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold).
This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion.
(Zhang et l. (2020))
- Among S variants tested, the D614G mutant shows the highest cell entry (~3.5x wild type), as supported by structural and binding analyses.
(Ozono et al. (2020))
- The increased transduction with Spike D614G ranged from 1.3- to 2.4-fold in Caco-2 and Calu-3 cells expressing endogenous ACE2 and from 1.5- to 7.7-fold in A549ACE2 and Huh7.5ACE2 overexpressing ACE2.
Although there is minimal difference in ACE2 receptor binding between the D614 and G614 Spike variants, the G614 variant is more resistant to proteolytic cleavage, suggesting a possible mechanism for the increased transduction.
(Daniloski et al. (2021))
Vaccine neutralization efficacy
- Using a lentivirus virus pseudotyped with D614G Spike, sera from vaccinated individuals who received the second dose (9–11 days post-second dose of Pfizer) exhibited a robust neutralizing potential, with a mean NT50 value of 99,000. This was an average of a 2-fold increase, relative to sera drawn from the individuals who received one dose of vaccination—mean NT50 dilution of 51,300. Importantly, a 6-fold increase in mean NT50 dilution was obtained when sera from the first vaccination dose was compared to convalescent sera from cohort with severe disease (NT50 51,000 vs 8,700) 21 to 63 days post-onset.
(Kuzmina et al. (2021))
- Pseudotyped D614G virus has reduced neutralization activity vs wild type: 1.2x (37 sera Pfizer median 9 days post 2nd dose, 37 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA.
(Garcia-Beltran et al. (2021))
- Hamsters infected with SARS-CoV-2 expressing spike(D614G) (G614 virus) produced higher infectious titres in nasal washes and the trachea, but not in the lungs, supporting clinical evidence showing that the mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increase transmission.
(Plante et al. (2020))
- Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion.
(Zhang et al. (2020))
- CryoEM shows increased proportion of "one-up" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2.
(Yurkovetskiy et al. (2020))
- Negative stain EM shows increased proportion of "one-up" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2.
(Weissman et al. (2020))
- Estimated free energy change (ddG) for this variant is 2.5 kcal/mol (i.e. stabilizing relative to wild type) (Spratt et al. (2021))
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