Sweeping the globe, did the D614G mutation really increase the spread of the new crown?

Today, the cumulative number of confirmed cases in the world’s new crown sits at 11 million, and the death toll is close to 520,000. Looking at the global outbreak of the new crown, scientists observed an interesting phenomenon: since late February, a mutated strain of the new crown virus began to sweep the globe. In just a few months, the proportion of patients infected with the mutated virus has grown from less than 5 percent to more than 90 percent today. It can be said that the vast majority of new crown infected people today are victims of this mutated virus.

Sweeping the globe, did the D614G mutation really increase the spread of the new crown?

A mutated new crown strain (G614 SARS-Cov-2, blue) began swept the globe in late February

On April 30, a paper on the mutated virus went live on the preprinted bioRxiv website, noting that a simple amino acid change makes the mutant virus “more spreading” and requires “urgent attention.” A week later, the paper caught the attention of the media and became a social media sensation. In the circle of friends, many with “watch out!” “The article also succeeded in mobilizing people’s anxiety and becoming a flashpoint.

Sweeping the globe, did the D614G mutation really increase the spread of the new crown?

Few people report that the preprinted paper was criticised by many scientists after it was published as “overblown” and lacked sufficient evidence to support it. Today, the paper is officially launched in the top academic journal Cell. Compared with its preprinted version, the paper has significant changes and a lot more complementary data. In today’s article, the academic team will also share the main points of the paper with your readers, as well as comments from all sides.

Mysterious D614G

Spike protein, the slobprotein, is the “city hammer” of the virus’s invading cells and is targeted by many vaccines and therapies. As a result, mutations in the stingprotein have also attracted the attention of many scientists — mutations that can change the properties of the stinging protein, make it easier for viruses to invade cells, or make vaccines and drugs ineffective.

Sweeping the globe, did the D614G mutation really increase the spread of the new crown?

(Photo credit: Jason McLellan/Univ. of Texas at Austin)

The scientists in charge of the study have developed a bioinformatics tool that can monitor new coronaviruses in different regions, what variations in their stingproteins, and how prevalent the different variants are. The study found that the new crown virus is not “a hundred flowers in full bloom”, but “a single family.” In various countries and regions, a strain of the virus with the “D614G” mutation dominates the position.

D614G refers to a variation of an amino acid. In the earliest emerging neo-coronavirus sting protein, the position 614 occupied is a domide (D). After the mutation, the position becomes glycine (G).

Sweeping the globe, did the D614G mutation really increase the spread of the new crown?

New crown strain (blue) with D614G mutation becomes absolutely mainstream on all continents

Looking back on the history of the mutation, scientists found that by March, it was far from becoming a global mainstream, accounting for only 10 per cent of the sequences measured globally. After expanding its influence in Europe, that figure jumped to 67% in March. At the paper’s data cutoff point, the proportion is as high as 78%.

The mutated virus did not erupt simultaneously globally, but followed the Order of Europe-North America/Oceania-Asia.

Impact of variation

In the preprinted paper, the researchers speculated a lot about the reasons behind this phenomenon, and suggested many potential causes of the D614G variant of the virus, such as affecting the structure of the stingprotein, affecting immunity, and so on. In the Cell paper, this space is significantly reduced. A variety of explanations in several lines of text in the district also indicate the author’s uncertainty about the reasons behind it.

Instead, the authors have done more research and exploration of the clinical consequences of this mutation. They analyzed the prognosis of 999 patients (almost double the 470 in the preprinted version) and found that the virus had a higher viral load in patients than before the mutation. There is no significant difference in the severity of the disease.

Sweeping the globe, did the D614G mutation really increase the spread of the new crown?

Cell experiments show that the new coronavirus strain (blue), which has d614G mutation, is more capable of infecting cultured cells

What’s more, the researchers found in cell experiments that fake viruses with this mutation (not using real neo-coronaviruses to do experiments, but only to make experimental viruses express the stinging protein) more capable of infecting cells. “Compared to virus particles with The D variant, the ability to infect cells is 3-6 times higher,” said one of the study’s authors. “

Is the D614G variation really “more propagative”?

From the above results, we can see that when the new coronavirus sting protein appears D614G mutation, the virus can more effectively infect the cells in the petri dish, the patient’s body also increased the viral load. In fact, the mutated virus did sweep the globe. Doesthis mean that the D614G mutation makes the new crown virus “more spreadable”?

Sweeping the globe, did the D614G mutation really increase the spread of the new crown?

Not also. Today, the journal Cell also published an op-ed devoted to explaining and discussing the results of the study. It is a fact that the new coronavirus with the G variant has become a dominant strain in many countries and regions around the world. However, while the paper gives evidence that the D614G variant is more “infectious”, the evidence is not enough to suggest that the mutated virus is more “contagious”.

Because another plausible explanation is simpler: it’s only a coincidence that the D614G-variant virus is sweeping the globe.

In February, the centre of the global new crown explosion moved from Asia to Europe. In March, North America became the center of a new outbreak. Many studies, including this paper, confirm that most of the new coronavirus strains in the United States are from Europe. And whether a particular strain of virus can become popular, not only with the virus itself transmission capacity, but also related to the number of times the virus was introduced. When most strains fail to make waves for a variety of reasons, such as the isolation of infected people, the few strains introduced multiple times will be “winner-take-all” and become the absolute mainstream.

In addition, the authors of the commentary note that at a time when the virus is gradually having an impact on the world, it coincides with the remarkable results of China’s anti-epidemic efforts, resulting in a rapid decline in the proportion of viruses that have not mutated. It also explains why the D614G variant can sweep the globe – it may simply be no other rival, and it doesn’t mean it’s more spreading.

Limitations in research

Both the author of the Cell paper and the author of the commentary article also point out that there are limitations in the study. For example, the study used not really the new coronavirus, but the fake virus, not necessarily representative. In vitro cell experiments that support increased infection cell capacity are also used in human kidney cell lines, not cells from the respiratory tract. From this point of view, the significance of the experimental results is not clear.

Sweeping the globe, did the D614G mutation really increase the spread of the new crown?

PharmaMing Kant Content Team Mapping

Moreover, viral infection strains rely not only on a sting protein in the region, but on the involvement of many other viral proteins and host proteins. None of these details has been discussed in this study. Therefore, we can not at all through a simple in vitro cell experiment, the assertion that a simple amino acid variant can have an important impact on a wide range of people.

“In vitro data in this study reinforce clinical findings that suggest d614G variants may replicate at higher levels in human cells. But we can’t say that this mutation makes the virus more spreadable or causes more serious diseases. The point is, we don’t know if it means anything to the new crown. One of the authors of the review article said.

Summarize

“Infectious” does not mean “transmission”, and we don’t need to have additional panic about this mutation. In an epidemic, it is normal for the virus to mutate. “Some variations can change the nature of a virus, but it doesn’t suddenly pose a huge threat to a virus like a switch.” One of the authors of the commentary added. At present, the effects of this mutation on vaccines and drugs are not important.

But we also need to note that whether the mutated virus is a random event or a natural selection, the strain is currently prevalent globally. Therefore, we need more research to better understand the nature of the virus and to help end the new crown outbreak as soon as possible. Rather than unnecessarily causing anxiety because of exaggerated conclusions, this may be the direction we should really focus on.