D614G mutation: Does it indicate that the virus is spreading out of control and that the vaccine is failing?

On July 3, 2020, a study in cell magazine showed that 29% of the new coronavirus samples showed a D614G mutation, and that the virus with that mutation had already spread in Europe and the Americas, and that the ability to infect cells had increased, did it indicate increased viral transmission and a risk of failure for vaccines that have not yet been made available? In particular, the outbreak in Beijing found in the rebound of the virus strain also has this mutation, the follow-up will be China's outbreak will have what kind of impact? What is a D614G mutation? The wide host nature of coronavirus and the structural characteristics of its own genome make it prone to genetic recombination and genetic diversity during evolution.
D614G mutation refers to the mutation of the new coronavirus's 614 amino acid bits D (tiantinine) to G (glycine), located in the S protein (Figure 1).
strains with D614G mutations are often accompanied by C-to-T mutations in 5'UTR (241 bits relative to the MN908947.3 genome), C-to-T mutations in 3037 bits, and C-to-T mutations in 14408 bits.
single-fold type containing these four genetic chain mutations is now a global dominant form, and according to the results of the new coronavirus sequencing published in the GISAID database, the strains carrying the mutation were found to be classified mainly as G, GR and GH.
so concerned about the D614G mutant strain? So far, more than 10,000 different bit mutations have been found in all new coronavirus genome sequences published on the GISAID database, but the D614G has attracted widespread attention.
1) Range, number and proportion of transmission: Until March this year, the strains carrying the mutation were far from mainstream worldwide, accounting for less than 10 per cent of the published sequence of virus strains worldwide.
spread to North America, Oceania, South America and Asia after its earliest discovery in Europe, the number soared to 60-70% throughout March.
more than 90 per cent by the end of June.
, the strain carrying the mutation has become the main genotype of transmission (Figure 2).
2) Potential functional aspects: The D614G mutation is a mistranslated mutation (a mutation that alters amino acids) and is located on the spike protein (S protein) of the new coronavirus (Figure 3), which is the core weapon for the new coronavirus to invade human cells and is currently the focus of many vaccines and therapies.
, mutations in the prickly protein are more likely to attract the attention of many researchers -- mutations that can alter the structure, properties, and vitality of the tinge protein, making it easier for viruses to invade human cells.
why does the D614G stand out and sweep the globe? The strain, which carries the D614G mutation, was first discovered in February, but did not occur simultaneously on a global scale, with the D614G mutation appearing early in Europe, when it accounted for less than 10% of the global sequence of new coronavirus sequencing before spreading to North America, Oceania, South America and Asia, becoming the main genotype of transmission after more than four months.
this phenomenon because the mutation alters the activity of the prickly protein, increasing the "aggressive" and "spreading" of the virus, making it easier for the virus to invade human cells? Subsequent articles published in cell, also using in-body infection experiments to calculate the viral load found that the D614G mutant virus load is higher.
, several teams found increased infection with D614G mutations in human lung endoculum cells and hACE2 cells.
But a commentary published in the journal Cell at the same time noted that the new coronavirus, which does have a D614G mutation, has become a dominant viral strain worldwide, and also gives experimental results that support the D614G variant to improve the ability of the new coronavirus to infect cells.
whether the D614G mutation will enhance the ability and toxicity of new coronavirus infections in humans remains uncertain and requires more clinical data support.
these tests do not take into account the effects of other viruses or host proteins, as well as the interactions between hosts and pathogens, to support infection and transmission.
the increase in the frequency of G614 necessarily be associated with an increase in propagation? Not necessarily! It may also be explained by the epidemiological chance of a pandemic.
, the outbreak in China was contained, cases in Europe became mainstream in the world, cases in the United States became mainstream again in March, and the vast majority of SARS-CoV-2 in the United States came from Europe.
whether virus types can be established in an area is related not only to transmission, but also to the number of times they are introduced.
Therefore, after China's domestic prevention and control stability, strengthen the prevention and control of importation, in the G614 became the world's majority variant of the period, with D614 still dominant China because of control of the spread of imported cases, the number of virus introductions in a sharp decline.
the D614G mutation was found in the Beijing outbreak, the G614 virus has lost the opportunity to expand significantly in China as a result of rapid and decisive prevention and control measures.
At the same time, China's anti-epidemic efforts have achieved great results, resulting in the D614 strain in the domestic transmission of effective control, the proportion in the world is getting smaller and smaller, D614G mutant strain in Europe and the Americas in the transmission process without other competitors, resulting in a unique status quo.
new coronavirus strain carrying the D614G mutation "more toxic"? Korber and others found higher levels of viral RNA in patients infected with the G614 mutant virus in COVID-19 cases in the UK, but no differences were found in hospital admissions.
some scholars have suggested that D614G mutation and disease mortality are strong correlation, but still remain in the statistical correlation analysis.
first of all, the severity of the disease cannot be measured by viral RNA load alone, and there are high titration viruses in asymptomatic infections, and the above analysis is related statistical analysis, there is no clear evidence.
, current evidence suggests that D614G is less important to COVID-19 than other risk factors, such as age or other underlying diseases.
, it is not possible to prove that the D614G mutant strain is more toxic.
the D614G mutation affect current testing, treatment, and vaccine research? Nucleic acid detection is currently recommended for the selection of open reading frame 1ab (open reading frame, ORF1ab) for new coronavirus, nucleoprotein (N) gene region primer and probe.
according to WHO guidelines, N3 in the 2019-nCoV lead and probe group design is used for universal detection of SARS-like coronavirus, N1 and N2 are used for specific detection of SARS-CoV-2, so the D614G mutation does not affect the nucleic acid detection of the virus.
binding region (RBD) of prickly proteins is currently the focus of many vaccines and therapies, and D614G is not located in the RBD region.
at the same time, naturally infected antibodies produced by viruses containing D614 or G614 can be cross-harmony, so for now, the D614G mutation is unlikely to have a significant impact on the efficacy of the vaccine currently under development.
, there is no evidence that the D614G mutation interferes with treatment strategies, such as designing drugs that destroy monoclonal antibodies that bind to ACE2's spike.
, however, any vaccine or treatment design should take into account the presence and possible effects of the mutation before we better understand the role of D614G in natural infection with SARS-CoV-2.
In the mutation of the new coronavirus, the D614G mutated strain "stands out" because of its spread and potential function, however, the virus strain continues to mutate, there is no sufficient evidence to prove that the D614G mutated strain is infectious, the toxicity has been strengthened, has not yet been observed on the vaccine and detection of important effects, the follow-up needs more experimental verification and monitoring of the phenomenon of mutation.
Reference 1. Korber B, Fischer W M, Gnanakaran S, et al. Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell, 2020.2. Grubaugh N D, Hanage W P, Rasmussen A L. Making sense of the mutation: What D614G means for the COVID-19 pandemic remains snr. Cell, 2020.3. Zhang L, Jackson C B, Mou H, et al. The D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivity. bioRxiv, 2020.4. Daniloski Z, Guo X, Sanjana N, et al. The D614G mutation in SARS-CoV-2 Spike increases transduction of multiple human cell types. bioRxiv, 2020.5. Becerra Flores M, Cardozo T. SARS-CoV-2 viral spike G614 mutation exhibits higher case fatal rate city. International Journal of Clinical Practice, 2020. Zhang Yi, Jiang Ning, Zhang Wenhong Source: Huashan Infection Copyright Notice: All text, images and audio and video materials on this website that indicate "Source: Mets Medicine" or "Source: MedSci Original" are owned by Mays Medical, are not authorized, may not be reproduced by any media, website or individual, and must be reproduced with the words "Source: Meis Medicine".
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