The D614G amino acid mutation in the SARS-CoV-2 Spike protein emerged early during the COVID-19 pandemic, quickly becoming the dominant circulating strain of the coronavirus. The transition from D614 to G614 occurred asynchronously in different regions throughout the world, beginning in Europe, followed by North America and Oceania and then Asia (Korber et al., 2020). Virus mutations may increase in frequency due to natural selection, random genetic drift, or features of recent epidemiology and as such it can be difficult to differentiate when a virus mutation becomes common through fitness or by chance (Korber et al., 2020). The mutation is located on the Spike protein, in the interface between the individual spike protomers, that stabilize its mature trimeric form on the virion surface through hydrogen bonding (not in the receptor-binding; RBD) (Grubaugh et al., 2020). The Spike D614G amino acid change is caused by an A-to-G nucleotide mutation at position 23,403 in the Wuhan reference strain. It is almost always accompanied by three other mutations: a C-to-T mutation in the 50 UTR (position 241 relative to the Wuhan reference sequence), a silent C-to-T mutation at position 3,037, and a C-to-T mutation at position 14,408 that results in an amino acid change in RNA dependent RNA polymerase (RdRp P323L). The haplotype comprising these 4 genetically linked mutations is now the globally dominant form (Korber et al., 2020).
The G614 variant grows to a higher titer as pseudotyped virions and in infected individuals may be associated with higher upper respiratory tract viral loads, but not with increased disease severity. Despite finding that clinical samples from G614 infections have higher levels of viral RNA, it’s still not clear if G614 is more infectious or transmissible than viruses containing D614. However, if it is the case that the mutation aids transmissibility, then the virus will be harder to control (Korber et al., 2020). The mutation has also been associated with increased sensitivity to neutralization of SARS-CoV-2 pseudoviruses in vitro and may stabilize a particular conformational state of the RBD (Weissman et al., 2020). Spike-pseudotyped lentivirus and intact SARS-CoV-2 virus in which the D614G mutation was introduced have been found to be up to 8-fold more effective at transducing cells than wild-type virus, in multiple cell lines, including human lung epithelial cells. Minimal differences in ACE2 receptor binding was observed between the Spike variants, but the G614 variant was more resistant to proteolytic cleavage in vitro and in human cells, suggesting a possible mechanism for the increased transduction (Daniloski et al., 2020; Huang et al., 2020).
Source:Recombinant protein corresponding to aa1-674 from SARS-CoV-2 Spike Glycoprotein, fused to a sheep Fc-Tag at C-terminal, expressed in HEK293 cells, containing both D614G and G485R amino acid changes relative to the Wuhan-Hu-1 isolate. The D614G isolate has been reported to show ncreased virus transmissibility.
Molecular Weight:~130kD
Storage and Stability:Aliquot to avoid repeated freezing and thawing and store at -70°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.
