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What is the Coronavirus mutation that shocked Britain?

New will be coronavirus (SARS – CoV – 2), the British government announced on December 19 to south-east England, including London, level 4 blockade, which means that people in these areas must stay at home, can’t even Christmas party with other families.

This new variation is primarily N501Y, a key amino acid mutation in the Novel coronavirusS protein receptor binding region (RBD).
Studies have shown that this makes it easier for a novel Coronavirus to bind to ACE2, the recipient of the novel Coronavirus, thus giving it the potential to accelerate the transmission of a novel Coronavirus.

Stuart Neil, a virologist at King’s College London, said the mutated virus had been linked to only 10 to 15 per cent of cases a few weeks ago. Last week it accounted for 60 per cent of cases in London.

Britain ended its second four-week lockdown on December 2nd, but the number of new infections rose rapidly after a brief dip in late November.
The number of confirmed COVID-19 cases in the UK reached 35,928 on December 20, surpassing the peak before the second closure and reaching the highest level since the outbreak began.
The picture shows the number of new coronavirus cases (left) and deaths (right) recorded by the UK government in a single day.
Photo source: https://coronavirus.data.gov.uk/

On 13 December, nearly 60 local authorities in the UK confirmed 1108 cases of a novel Coronavirus that had produced the mutation, while the actual number of infections may be much higher.

So what does this new variation mean?
What is the impact on the current epidemic prevention and control?
Will it affect the efficacy of the COVID-19 vaccine that is coming on the market?

1

British novel Coronavirus appears variant

As RNA viruses, it is not surprising that novel Coronavirus appears a new variant.

“Genetic mutations in viruses are permanent, and all the mutations we can detect are those that survive and spread successfully.”
Shi Zhengli, a researcher at the Wuhan Institute of Virology under the Chinese Academy of Sciences, who has been studying coronavirus for years.

Since the first novel Coronavirus genome sequence was uploaded to the database, scientists have been monitoring the evolution of the novel Coronavirus in real time.

In general, a new variant gets attention, either because of a sudden increase in the frequency of the cycle, such as the European D614G variant, and subsequent experimental evidence suggests that infectiity does increase;
Either the clinical features are significantly altered, as in the earlier OrF8-deletion variant in Singapore, which subsequent trials have shown to be less pathogenic.

These clinical changes are visible to the naked eye, but more experiments are needed to determine whether the immunological characteristics induced by these changes are altered.
According to the mutation degree of most novel Coronavirus strains at present, the induced immune response has not changed significantly.

This novel Coronavirus new variant from the UK was discovered by monitoring the database.
According to its mutation characteristics, it was divided into a new branch in phylogenetic tree B.1.1.7.
Over the past four weeks, the frequency of the spectrum has increased rapidly and continues to spread across the UK.

The original two, one from Kent on 20 September 2020 and the other from Greater London on 21 September 2020.
By the beginning of December 2020, b.1.1.7 lineage infections were continuing to be detected in the UK, and by 15 December, 1623 genome sequences had been uploaded, 519 in greater London, 555 in Kent, 545 in other parts of the UK (including Scotland and Wales) and four in other countries.

“There is no data to suggest that this was brought in from abroad,” said Nick Loman, professor of microbial genomics and bioinformatics at the University of Birmingham. “It may have evolved within the UK.”

B.1.1.7 Phylogenetic trees and mutation sites of the pedigree

For will be coronavirus, mutations over time, with basic constant speed accumulation of mutations (about 1 to 2 times a month), at present most of the mutant strains compared with the original strain several commonly, but b. 1.1.7 spectrum accumulation of many mutations, there are mainly six synonymous mutations, 14 non-synonymous mutations and three missing mutations, evolution velocity anomaly, and the roots of far distance.

At present, the source of this pedigree is unknown, and it is speculated that it may be caused by chronic infection of immunodeficiency patients or selective pressure of drugs such as plasma of rehabilitative patients or redesivir. There is also previous evidence that selective pressure will lead to the accelerated evolution of novel Coronavirus.

Maria Van Kerkhove, who’s technical director for the COVID-19 response, said the mutation had been monitored by the WHO’s working group on viral evolution.
“This variation is related to variants found elsewhere in mink.”

B.1.1.7 Regression analysis of genetic distance between lineages (blue) and outgroup lineages (brown) sequences in phylogenetic trees to the sampling date

2

What does the new variant mean?

Specifically, what happened to the new variant of the virus in the UK?

Among the mutations in the b. 1.1.7 lineage S protein, the most notable mutation site is the key amino acid mutation N501Y in RBD (receptor-binding region), which is particularly important.
On 30 July this year, Chinese scientist Yu Sen Zhou et al. published in Science that novel Coronavirus adapted and infected wild-type mice due to the N501Y mutation.
The mutation greatly increased the affinity between RBD and receptor ACE2 and enabled the novel Coronavirus strain that was not originally infected mice to become able to infect mice.

In September this year, according to a paper published in Cell the Fred hutchinson cancer research center and the university of Washington scientists found that will be coronavirus receptor area quite a lot of to enhance the ability to combine with ACE2 amino acid mutations, which forecasts the loci N501F/T mutation enhanced ACE2 affinity with people, but they had no evidence that circulating strains produced these mutations.

Is another notable mutations in the structure of n-terminal domain (NTD) H69 coupe and the V70 station wagon deletion (del), 69-70, the variations in July at the earliest, Britain, the Netherlands, Australia also are seen, later in the Danish mink frequently caused wide public concern, which together with Y453F appear in mink, whereas in humans often appear together with N439K.
Studies have shown that the 69-70DEL mutation can escape the neutralization effect of some monoclonal antibodies, and may also reduce the neutralization sensitivity of some serum.

The mutation of P681H in S protein may also have a potential influence on the characteristics of virus. This site is close to the S1/S2 Furin cleavage site of S protein, and the Furin cleavage site is crucial to the novel Coronavirus infection of host cell, so it is speculated that P681H may also have an influence on the infectiousness of coronavirus, but there is no clear experimental evidence yet.
In addition, other mutation sites in S protein have little effect on function and have not yet aroused attention.

In addition to The S protein, the Q27stop mutation in ORF8 leads to the premature end of ORF8 protein coding and loss of function.
In the early stages of the pandemic, several ORF8 deletion mutant strains were isolated globally and described in several studies, which slightly affected replication in primary human airway cells and were associated with less clinical infection and less post-infection inflammation, i.e., reduced pathogenicity.

To date, other mutation sites have not been clearly described.
It is important to consider that the specific function of the new variant should take into account the combined results of all the mutants, given that the new variant contains multiple mutants. There is no conclusive evidence of the effect of the new variant on virological and immunological properties.

In the CASE of the UK, it is likely that the D614G variant will significantly increase infectivity, and more experimental evidence is needed to determine whether it affects pathogenicity and immune escape.

According to the minutes of a meeting of the UK’s Advisory Group on the Crisis of Emerging Respiratory viruses on 18 December, the rate of new infections was 71 per cent higher than that of other strains.

Matt Hancock, the health secretary, stressed there was no indication that the new virus would cause more severe disease or that the vaccine would no longer work.

It is important to note that most of the current leading vaccines use S protein as the immunogen and contain multiple epitopes to induce polyclonal antibody serums. Even if some mutant sites can escape monoclonal antibodies, it will not have a significant effect on the neutralization of the whole serum.
The Science paper, for example, shows that a strain with an N501Y mutation can still be neutralized by a novel coronavirusRBD specific neutralizing antibody.

Jiang Shibo, director of the Institute of Pathogenic Microbiology at Fudan University, told The Intellectual: “Vaccine and antibody developers should try the mutated virus as soon as possible to see if their vaccine developed antibodies are less sensitive to this?
If it’s worth noting, that’s critical.”

Jiang added that studies should be conducted as soon as possible to see if the pathogenicity of the mutant strain increases. “If it increases pathogenicity, it may increase its lethality in the future,” he said.

3

Countries have taken to isolating Britain

Britain, which first discovered the novel coronavirus variant, immediately embarked ona new round of epidemic prevention and control.

From December 20th, the south-east of England, including London, was upgraded to level 4 lockdown.
Compared with the previous level 3 measures, under the new control, all entertainment venues such as non-essential shops, barbershops and gyms will be closed. In addition to education, taking care of children, exercising, shopping or not being able to work from home, people in this area should stay at home as far as possible. Different families are not allowed to gather, and only one-on-one meetings are allowed in public places.

The measures will remain in place until December 30, when the government will review them again.
For the UK, that means there will be no parties, no Christmas markets and no Boxing Day shopping extravaganza.
Areas outside the lockdown will be relaxed on Christmas Day, December 25, under the original controls.

Outside the UK, many countries have announced bans or suspensions on entry from the UK.

On 20 December, the Netherlands first announced a travel ban on the UK, which will remain in place until at least 1 January 2021.
In addition, Germany, Ireland, Belgium, Austria, Switzerland, Portugal, Finland, Croatia, Bulgaria, Italy, Sweden, Romania, Estonia, Latvia, Lithuania, Canada, India, Israel, Iran, Saudi Arabia, Turkey, Morocco, el Salvador, Colombia and Kuwait also announced to the British travel ban to varying degrees.

Across the sea from The UK, France suspended passenger and cargo traffic from the UK for 48 hours starting at 23:00 GMT on December 20.
The decision will also affect the channel tunnel linking Kent with France, which is used by Eurostar trains and vans carrying food and household goods imported from Britain.

Matthew Hancock, the UK health secretary, said domestic restrictions were likely to remain in place for months until the vaccine was fully introduced.

The UK has procured 40 million doses of Pfizer vaccine to give priority to the elderly and health workers.
Grant Shapps, Britain’s transport minister, said in an interview with Sky News on December 21 that the French ban would not have any impact on vaccination in the UK.

Although the reported variants may not affect the efficacy of the existing vaccines, it will be a continuing test for countries how to coexist with viruses from a novel Coronavirus and how to deal with other variants that may arise from viruses from a novel Coronavirus.

“Or there could be a global effort to hunt it down, plus a vaccine, to get rid of it like smallpox and poliovirus, but at the cost of economics.
Or you can have a mild isolation and live with it like a flu virus.”
On the future of human and novel Coronavirus, Shi zhengli explains to The Intellectual.

“The dilemma is that there is no global consensus on how to deal with the epidemic.”
“She added.

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