Zhang Wenhong and others talk about D614G mutation: Whether it indicates that the virus spreads out of control and the vaccine fails.

This article is reproduced from "Huashan infection".preface on July 3, 2020, a study in cell Magazine showed that 29% of the new coronavirus samples had d614g mutation. The virus with this mutation had already spread in Europe and America, and the ability to infect cells was enhanced. Does it indicate that the virus transmission capacity is enhanced and the vaccine that has not yet been put on the market is at risk of failure? In particular, the virus strain found in the rebound in Beijing also has this mutation. What kind of impact will the subsequent epidemic situation have on China? What is d614g mutation? Because of the wide host nature and the structural characteristics of its own genome, coronavirus is prone to gene recombination and genetic diversity in the process of evolution.d614g mutation refers to the mutation from D (aspartic acid) to G (glycine) in amino acid 614 of new coronavirus, which is located in S protein (Fig. 1).d614g mutation was associated with C to t mutation in 5'UTR (compared with 241 in mn908947.3 genome), 3037 C-T mutation and 14408 C-T mutation.the haplotype containing these four genetic linkage mutations has become the dominant form in the world. According to the sequencing results of the new coronavirus published by the gisaid database, it was found that the virus strains carrying the mutations were mainly classified into G type, GR type and GH type. The d614g mutation in the sars-cov-2 spike protein reductions S1 shelving and increases effectiveness [J]. Biorxiv, 2020.)? Up to now, more than 10000 different site mutations have been found in all new coronavirus genome sequences published in gisaid database, but d614g has attracted extensive attention.1) transmission range, number and proportion: before March this year, the virus strains carrying this mutation were far from becoming the global mainstream, accounting for less than 10% of the published sequencing sequences of virus strains in the world.it was first discovered in Europe and then spread to North America, Oceania, South America and Asia, and the number soared to 60-70% in March.by the end of June, it had been over 90%.therefore, the virus strains carrying this mutation have become the main genotype of transmission (Fig. 2).Figure 2 (source: korber B, Fischer w m, gnanakaran s, et al. Tracking changes in sars-cov-2 spike: evidence that d614g increases effectiveness of the covid-19 virus [J]. Cell, 2020.; daniloski Z, Guo x, sanjana n, et al. The d614g mutation in sars-cov-2 spike increases transmission of multiple human cell types [J]. Biorxiv, (2020.) 2) potential function: d614g mutation is a missense mutation (change of amino acid mutation), and the mutation is located on spike protein (s protein) of new coronavirus (Figure 3), which is the core weapon of new coronavirus invading human cells, and is also the focus of many vaccines and therapies.as a result, mutations in spindles are more likely to attract the attention of many researchers - these mutations may change the structure, properties and activity of spindles, thus making it easier for viruses to invade human cells.Figure 3 (pictures from the Internet) why does d614g stand out and sweep the world? The strain carrying the d614g mutation was first discovered in February, but it did not occur at the same time worldwide. The d614g mutation appeared in Europe in the early stage, accounting for less than 10% of the global NCV sequencing sequence at that time, and then spread to North America, Oceania, South America and Asia. After more than four months of transmission, it has become the main genotype of transmission.is this phenomenon because the mutation changes the activity of spike protein and improves the "aggressiveness" and "transmissibility" of the virus, thus making it easier for the virus to invade human cells? In subsequent articles published in the cell, we also calculated the viral load after in vitro infection experiment, and found that d614g mutant had higher viral load.in addition, several teams have found that d614g mutation has enhanced infectivity in human lung epithelial cells and hace2 cells.however, a review article published at the same time in cell magazine pointed out that the new coronavirus with d614g mutation has become the dominant virus strain in the world, and the cell experiment results supporting the d614g mutation to enhance the infection ability of new coronavirus are also given. However, it is still uncertain whether d614g mutation will enhance the ability and toxicity of new coronavirus infection in humans, and more clinical data are needed.these tests do not take into account the effects of other viruses or host proteins, and the interaction between host and pathogen to support infection and transmission.is the increase of g614 frequency necessarily related to the increase of transmission? not always! It may also be explained by the epidemiological contingency of the pandemic. after February, the epidemic situation in China was under control, and European cases became the mainstream in the world. In March, the majority of sars-cov-2 lineages in the United States came from Europe. whether virus typing can be established in a region is not only related to transmission, but also to the number of times they are introduced. therefore, after the stability of domestic prevention and control, China should strengthen the prevention and control of import. During the period when g614 became the majority of varieties in the world, the number of imported viruses in China, which was still dominated by d614, was declining sharply due to the control of the transmission of imported cases. although the d614g mutation was found in the Beijing epidemic, the g614 virus lost the opportunity to greatly expand in China due to the rapid and decisive prevention and control measures. at the same time, great achievements have been made in China's anti epidemic work, leading to the effective control of the spread of d614 virus strain in China, and the proportion in the world is becoming smaller and smaller. There is no other competitor for the d614g mutant virus strain in Europe and America, which leads to the dominant situation. is the new coronavirus strain carrying d614g mutation more virulent? Korber et al. Found that patients infected with g614 mutant virus had higher viral RNA levels in covid-19 cases in the United Kingdom, but there was no difference in hospitalization results. some scholars have proposed that d614g mutation has a strong correlation with disease mortality rates, but still stays in the statistical correlation analysis. first of all, viral RNA load can not be used to measure the severity of the disease. High titers of virus also exist in asymptomatic infected patients, and the above analysis is related statistical analysis without clear evidence. at the same time, current evidence suggests that d614g is less important for covid-19 than other risk factors, such as age or other underlying diseases. therefore, the current evidence cannot confirm that the d614g mutant is more virulent. will d614g mutation affect current detection, treatment and vaccine research? Nucleic acid detection novel coronavirus is currently recommended for open reading frame 1ab (open reading frame, ORF1ab) and core shell protein (nucleoprotein, N) gene primers and probes. according to WHO guidelines, N3 is used for universal detection of SARS like coronavirus, and N1 and N2 are used for specific detection of sars-cov-2. Therefore, d614g mutation does not affect the nucleic acid detection of the virus. the receptor binding region (RBD) of spinin is the target of many vaccines and therapies, and d614g is not located in RBD region. at the same time, antibodies produced by naturally infected viruses containing d614 or g614 can be cross neutralized. Therefore, it is unlikely that d614g mutation will have a significant impact on the efficacy of vaccines currently being developed. in addition, there is no evidence that d614g mutations interfere with therapeutic strategies, such as designing drugs that destroy monoclonal antibodies that bind to the spike of ACE2. however, before we can better understand the role of d614g in the natural infection of sars-cov-2, any vaccine or treatment design should take into account the existence and possible impact of the mutation. among the new coronavirus mutations, d614g mutant virus strain "stands out" due to its transmission and potential function. However, the virus strain continues to mutate. There is no sufficient evidence to prove the infectivity and toxicity of d614g mutant virus strain, and no significant impact on vaccine and detection has been observed. More experiments are needed to verify and monitor the mutation phenomenon in the future. [1] tracking changes in sars-cov-2 spike: evidence that d614g increases effect of the covid-19 virus [2] Rasmussen a L. making sense of mutation: what d614g means for the covid-19 extensive remains unclear [3] the d614g mutation in the sars-cov-2 spike protein reduces S1 shedding and increases infectivity[4] The D614G mutation in SARS-CoV-2 Spike increases transduction of multiple human cell types[5] SARS‐CoV‐2 viral spike G614 mutation exhibits higher case fatality In the past, gerontology: Retina "recharges" for 3 minutes to save vision loss over 40 years old hot article PNAs: Chinese scholars found a new recombinant swine influenza virus with pandemic potential. 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