How the mutant novel coronavirus has changed the world epidemic?

To win the battle against novel coronavirus, we need to understand what causes the emergence of novel mutants, and what those mutations mean

Sina science and technology news Beijing time on February 3, in the contest that lasts for more than a year with novel coronavirus, human encountered a lot of challenges.
Vaccines offer hope, but new mutations are a source of concern.
To win this protracted battle, we need to understand what drove the novel coronavirus mutant, and what those mutations mean.

In the early days of the novel coronavirus, it somehow acquired the ability to profoundly affect human health.
A seemingly insignificant mutation in the virus’s genetic code was probably the result of an unfortunate accident when it and another virus infected a bat at the same time, and the genetic fragments of the two were mixed in the bat.

However, it was the instructions contained in this small piece of the genome that altered a key part of the virus, the Spike protein (S protein).
This important protein attaches to the outside of the coronavirus and can bind to receptors on the outside of the cell, helping the rest of the virus sneak inside the cell and replicate.

This mutation in the spiroprotein allows the novel coronavirus to hijack the protease, the furin, in humans.
The enzyme acts like a pair of molecular scissors, cutting through hormones and growth factors to activate them.
When the Flynn protease snips a portion of the novel coronavirus protein, which usually folds into a series of circular structures on the outside of the virus, the protein is opened like a hinge.

Yohei Yamauchi, a researcher in viral cell biology at the University of Bristol in the United Kingdom, who has been studying how this mutation could lead to novel coronavirus becoming more infectious to humans, said: “The process exposed a new sequence in the spiroprotein.
This is one of the changes that makes this virus very different from the previous coronaviruses that caused SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome).”

Scientists have been able to track the evolution of the virus in swab samples taken from the Covid-19 testing center

The new mutation also means that novel coronavirus could suddenly bind to a protein called Neuropilin 1, or NRP1, to invade cells.
This protein is located on the outside of human respiratory and olfactory epithelial cells and directs substances into cells and tissues.
In other words, the mutation provided a door key into cells for the novel coronavirus, allowing it to replicate in large numbers in the human respiratory tract.

Although this mutation has not been around for a long time in novel coronavirus, its importance is evident.
Some researchers believe this could be one of the key mutations that allow novel coronavirus to jump species and start spreading disease rapidly among humans.
Yet almost at the same time that Novel coronavirus spread rapidly, researchers began to find other mutations in it.

In almost every infected person, the virus changes very subtly — taking a letter from the genetic code here, deleting another letter there, or replacing it with a different letter, and so on.
These tiny errors usually occur when a virus takes over a cell’s molecular machinery to replicate.
Other than helping scientists track how the virus is spreading around the world, most mutations have little effect.
But in a few cases, the presence of a mutation can alter how quickly the virus spreads, or how infectious it is, or even the severity of the disease it causes.

As the Covid-19 pandemic continues, understanding the factors that may be driving certain changes in the virus, and the impact of those factors on the virus’s behavior, is critical.
Here are some of the most important mutations in novel coronavirus to date.

D614G mutation

The mutation that allows Flynn protease to cut off spikes was already present in the novel coronavirus when the outbreak began in early December 2019.
Just a few months later, Europe began to see its first cases.
By this time, the researchers found, novel coronavirus had undergone significant changes that had a significant impact on the course of the epidemic.

Although there is now evidence that novel coronavirus appeared in Europe as early as December 2019, the initial spread of the virus appeared in northern Italy in February 2020.
Samples collected from there on Feb. 20 showed that Novel coronavirus had a mutation in the spikula protein, leading to a dramatic increase in the number of viral particles released from infected cells, particularly from the patient’s upper respiratory tract.
The researchers called the mutation D614G, which is the dominant strain of the current global pandemic.
It is this mutation that appears to cause the virus to spread more quickly from person to person, possibly because infected people cough and exhale more of the virus.

Novel coronavirus British variant has several mutations in the spiroprotein, making it easier to bind to human cells

The D614G mutation provides a more “open” structure for the novel coronavirus spiroprotein, enhancing its ability to bind to the ACE2 receptor on the surface of human cells.
The ability of novel coronavirus to bind to ACE2 has been thought to be one of the reasons it was able to infect humans in the first place, and the new mutation gives the virus an enhanced ability to target human cells.

Subsequent studies have shown that the D614G mutant strain is more infectious than the novel coronavirus found in Wuhan and appears to be more common in young people.
But it comes at a cost — mutations can make the virus more vulnerable to antibodies, meaning it is less able to re-infect people who have been sick before.
On the other hand, it also means that convalescent plasma from patients who have recovered can be used to fight the virus.

Festival virus strain

Then, as the European blockade eased over the summer and international travel picked up again, another important new variant of novel coronavirus appeared in Spain.
The mutant strain was first identified in June 2020 and has since spread across Europe, accounting for 50 to 70 percent of cases in Switzerland, Ireland and the United Kingdom by September.

In the strain, named 20A.EU1, the researchers found a mutation called A222V in the spike protein.
But the mutation was not present in the area that binds to the cell surface, making it unlikely that it would lead to increased infectivity.
Instead, the researchers believe that the rapid spread and high prevalence of 20A.EU1 is more likely to be accidental, because it occurred at a time when restrictions were loosened and people were traveling more intensively during the summer holidays, when people were more in contact with each other.

Escape antibody

While the A222V mutation did not appear to lead to dramatic changes in the behavior of novel coronavirus, another mutation in Scotland in March 2020 sounded the alarm.
The mutation, known as N439K, was found in about 500 samples taken from patients in Scotland, but by June 2020 it appeared to have become extinct in Scotland, possibly due to a sharp drop in transmission due to strict blockade restrictions.

Not only did the mutation appear to enhance the ability of the novel coronavirus spike protein to bind to the ACE2 receptor on human cells, but the virus strain carrying the mutation also showed some resistance to antibodies taken from recovered patients.
That has raised concerns about the ability of the virus to re-infect, but experts say the strain should not make patients sicker.
A recent report from the Covid-19 Genomics Consortium (COG UK) added: “There is no evidence that this mutation enables the virus to weaken vaccine-induced immunity.”

However, in the autumn of 2020, a new case of the mutation emerged, apparently unrelated to the cases in Scotland.
The novel coronavirus mutation appeared elsewhere in Europe and in the United States, and continues to circulate in the United States today.
Now, the N439K mutation usually occurs in conjunction with another mutation that manifests itself as the loss of two distinct key amino acids, H69 and V70, in the spines.

Multiple mutations

In fact, novel coronavirus strains with H69/V70 deletion mutations have emerged worldwide.
The mutation was first detected in samples from Thailand in January 2020 and again in Germany in February, although the two discoveries do not appear to be related.

The loss of H69/V70 alters the shape of the novel coronavirus protein, making its circular structure more compact, the researchers found.
Although the benefits to the virus from this are not fully understood, it has been suggested that this may be an adaptation of the virus to try to evade the immune system, although the effect of the mutation on disease severity or vaccine effectiveness has not been found.

Ravinda Gupta, a clinical microbiologist at the University of Cambridge, UK, who was one of the first to identify the “B117” variant novel coronavirus, says the H69/V70 deletion mutation “increases infectivity by twice as much”.

Millions of minks have been culled in Denmark after a novel coronavirus mutant strain was found to be able to pass from animals to humans

Analysis of virus sequencing data from around the world revealed multiple H69/V70 deletion mutations in novel coronavirus.
The mutation spread quietly for most of 2020, and then a cluster of people infected with the mutated strain emerged in Denmark.
Upon investigation, the researchers found the mutation in a strain of the virus that was transmitted to humans from minks on farms.
Further analysis showed that the virus had mutated slightly, making it more infectious to animals, and some early data suggested that it was also less sensitive to antibodies contained in the serum of patients recovering from the new crown.

By August 2020, the H69/V70 deletion mutation began to become more common and appeared in viral samples along with the N439K mutation.

A mutated strain of the virus in the UK

The H69/V70 deletion mutation is also one of the main features of the rapidly spreading so-called “UK variant” strain, the B117 strain.
In addition, the B117 strain has accumulated 16 other mutations in its spines.
“There are a lot of mutations in this new mutant virus that we’ve never seen before,” Ravinda Gupta said.

One of them, a mutation near the Flynn protease cleavage site on the spikes, known as the P681H mutation, has previously been found in other variants around the world, including the B11207 strain that emerged in Nigeria in December.
The difference from the British variant is that the B11207 strain also carries another important mutation, called N501Y, which occurs in a key region where the virus binds to cells.
The researchers believe this mutation helps the virus bind more closely to the ACE2 receptor on the outside of the cell.

The exact impact of the other individual mutations seen in the UK strain is still to be explored, but when combined they are enough to make the virus more transmissible from person to person.
This may be because people infected with this variant produce more virus particles than previous people infected with the virus.
In other words, when a patient infected with the new variant coughs, speaks and breathes, more of the virus is expelled in droplets.

As the B117 strain spread rapidly in Britain, many countries temporarily closed their borders, leading to long queues for lorries

The scientists estimate that the B117 strain is replicating itself twice as fast as the original strain.
According to current projections by some public health officials, the B117 strain will become the dominant form of novel coronavirus in many countries, including the United States.
How exactly does this strain of the disease occur?
Scientists don’t yet know, but the idea that so many mutations don’t accumulate gradually, but suddenly come together, has given some researchers a clue.

“One possible hypothesis is that these mutations occurred in a chronic patient infected with the virus,” Ravinda Gupta said.
Among chronic patients infected with Novel coronavirus, at least two cases of H69/V70 deletions occurring simultaneously with other mutations occurred in an elderly woman in Moscow, Russia, and a man in Cambridge, England.

Both men had been treated for cancer, which is believed to have reduced their immune systems’ ability to fight novel coronavirus.
Because patients have been infected for a long time, the virus has had time to multiply and accumulate mutations in their bodies.
When they were treated with antibodies, those viruses that were better able to escape or resist treatment survived.
“We don’t yet know to what extent this happens with the B117 strain, but in a long-term infection, the virus has a chance to beat back the genetic stress that comes with treatment.”
Ravinda Gupta added.

Recently published mortality figures in the UK suggest that the B117 strain is 30 per cent more lethal than earlier viruses, but this has yet to be confirmed by peer-reviewed scientific studies.
Even so, Ravinda Gupta does not expect the B117 strain to pose a problem for the vaccine currently being rolled out around the world.
A recent study showed that antibodies produced by Pfizer vaccine trial participants appeared to work against the mutated strain.
“But it is a warning sign that we cannot be complacent,” he said.

South African virus strain

Shortly after news of the B117 strain emerged, South African scientists revealed that they had also discovered a new variant of another novel, coronavirus, circulating in the country.

“After the first wave of novel coronavirus, we are seeing a rapid resurgence in cases in two regions of South Africa – the Eastern Cape and the Western Cape,” said Carolyn Williamson, head of the department of virology at the University of Cape Town.
She and her colleagues stepped up virus sequencing in both regions and found that a new strain emerged in mid-October 2020 and quickly became the dominant strain by the end of November.
By December, the strain of the disease – known as 501Y.v2 or B1351 – had spread to many other parts of South Africa and was also found in neighbouring Zambia.
Since then, variants of the virus have been found in travelers from at least 20 other countries, and some countries are showing signs of local transmission.

A recent study showed that the South African mutant strain was able to escape antibodies in the plasma of people infected during the first pandemic.
Some may be concerned about the effectiveness of the current new crown vaccine against this variant, but it is important to note that antibodies are only part of the immune system’s response to the virus.
Other types of immunity, such as those provided by T cells, may still be effective, though this has yet to be tested.

Williamson and his colleagues also found that the new mutant strain carries eight unique mutations in the spike protein, three of which may make it more transmissible.
“We don’t know how this variant came to be,” Williamson said.
But she speculates that it may also have come from someone who has been infected for a long time. “Typically, novel coronavirus causes an acute infection that clears quickly…
But in some individuals, there may be continuous replication that allows the virus to evolve.”

Of all the mutations found by Williamson and her team, the N501Y mutation is also present in the British strain of B117.
Another mutation, K417N, has been found to bind to the N501Y mutation to increase the strength of the virus’s binding to the ACE2 receptor on human cells.
However, computer modeling studies have suggested that the K417N mutation may counteract the increased binding capacity seen in the N501Y mutation.

There is no indication that the South African strain will cause more severe disease, but it appears to be spreading faster than previous strains.
“Viruses that are more infectious and less pathogenic are more likely to survive,” Williamson said.
That’s because if the virus kills its host too quickly, it doesn’t have time to multiply more and spread to others.

However, studies have shown that the K417N mutation may reduce the susceptibility of the virus to human antibodies.
A third mutation, called E484K – which is not present in the UK strain – also appeared to reduce the virus’s vulnerability to antibodies.
One study showed that changes to the E484 site in the sphingin protein reduced the ability of some antibodies to neutralize it by a factor of 10.

Brazilian virus strain

E484K also turned out to be an important mutation in another worrisome novel coronavirus variant.
The strain, known as P1, is now circulating around the world.
The P1 strain contains 20 unique mutations, including the E484K mutation found in the South African strain.
According to investigation, the strain of the disease appears to have first appeared in the city of Manaus in the northern Amazon state of Brazil, which has been severely affected.
The P1 strain was also found in four passengers who flew from northern Brazil to Japan on January 2, 2021.

The P1 strain carries the E484K and K417T mutations as well as the N501Y mutations.
Although scientists are still studying the exact consequences of these mutations, the disease strain has been identified by health officials around the world as a “variant of concern.”

The new strain circulating in Brazil has shown signs of being able to re-infect people already infected

According to the U.S. Centers for Disease Control and Prevention, the emergence of a mutant strain of the Brazilian P1 virus has raised concerns that it could lead to a larger reinfection.
Two months ago, researchers found another Brazilian mutant strain, named P2, in patients infected with novel coronavirus.
However, while the disease strain carries the E484K mutation, it does not carry the other two mutations of the P1 strain.

The emergence of the E484K mutation has led many to fear that novel coronavirus may be evolving in a way that allows it to evade parts of the immune system, but scientists at the UK’s Covid-19 Genomics Consortium say there is no evidence that it affects the effectiveness of current vaccines.

As novel coronavirus continues to mutate, many virologists are looking for new ways to defeat the virus.
Michael Worobe, a viral evolutionary biologist at the University of Arizona in the United States, and his team are developing an “early warning” test that will try to identify a new strain of novel coronavirus as it begins to spread.

“We’ve got a lot of valuable information from laboratory studies about how certain changes in amino acids can be potentially dangerous,” Dr. Worobey said, “so we can take advantage of that and hopefully find them early.”
If the test is in use, it could help public health officials and vaccine manufacturers prepare for major new mutations in the virus.

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