Japanese Virologist: UK-Found Mutant Strain Is More Virulent

Recently, reports about the mutation of the new coronavirus have continued to appear around the world, making the mutation of the virus the focus of attention. In the United Kingdom, South Africa, Brazil, Denmark, the Netherlands, the United States, Australia, Canada, Italy, Iceland, Japan, China and other dozens of countries, infections caused by variants of the new coronavirus have been discovered.

Source: Xinhua News Agency

Will these newly emerging variants of the new coronavirus affect the spread of the virus? Will it cause aggravation after infection? Will it affect the effectiveness of the vaccine and hinder the anti-epidemic process?

With these questions in mind, a reporter from the Science and Technology Daily interviewed Kazuo Kitasato, an expert in virology at the Department of Pharmacy, Nagasaki University, Japan.

What is virus mutation? Is it getting better and better?

Kitari said that the genetic information of life on earth is carried by substances called nucleic acids. Nucleic acids are mainly divided into two categories, one is DNA (deoxyribonucleic acid) and the other is RNA (ribonucleic acid).

Viruses are parasitic microorganisms that only infect cells that invade organisms and use the raw materials in the infected cells to copy their genetic information to their descendants.

According to the genetic material carried by the virus, it can be divided into two main categories, one is the genetic material of the virus in the form of DNA, we call it DNA virus, the other is in the form of RNA, we call it RNA virus .

RNA generally exists in the form of a single strand (single-stranded), and a small part also exists in the form of double-stranded RNA. The new coronavirus is a single-stranded RNA virus. RNA is composed of four ribonucleotides A (adenine), U (uracil), C (cytosine), and G (guanine).

In the process of RNA virus replication, because the general RNA virus lacks a proofreading mechanism, it is prone to a higher error rate during virus replication, so the virus is very prone to mutation. It can be said that mutation during the replication process is common to almost all RNA viruses. Viruses generally exist naturally in some wild animals, and they must be mutated to break through the isolation of species when they can infect people, and enter human cells from natural animal hosts to reproduce.

It can be said that mutation is a survival strategy of the virus.

The mutation of viruses is generally random and directionless. Not all of these mutated viruses survive. If the mutation of the virus cannot help the virus adapt to the environment, then the virus will be eliminated. Because mutation will also reduce the virus’s ability to infect or even disappear completely, most of the virus mutations may be harmful to the virus itself.

The mutation of the new coronavirus S protein directly affects transmission

Kitasato said that the new coronavirus mainly infects cells through the binding of the spike protein (S) on the surface of the virus to the angiotensin converting enzyme 2 (ACE2) receptor on the surface of human cells.

The mutation of the S protein of the new coronavirus may directly affect the infectivity and transmission ability of the virus, as well as the effect of the neutralizing antibody produced by vaccination. Therefore, our focus here on the mutation of the new coronavirus is mainly on the virus S protein.

The S protein of the new coronavirus is composed of 1273 amino acids. According to a paper report in the internationally renowned journal Cell, at least 106 mutation sites have been identified for the S protein of the new coronavirus.

The D614G mutation refers to the amino acid at position 614 on the S protein, which has been changed from aspartic acid (D) to glycine (G). This mutation was produced in Europe before January 15, 2020. Before March 21, the 614th position of the S protein of the global new coronavirus strain was mainly D. After that, the 614th mutation of G became the main epidemic strain. .

Most viruses currently circulating in the world are strains with this D614G mutation.

The 614G mutation site is located in one of the six key contact residues in the cell receptor binding domain (RBD) of the S protein. The emergence of the D614G mutation causes the virus S protein to have an extra Elastase cleavage site. The infection and transmission capacity of the D614G mutant virus released from the cell has been increased by nearly 10 times.

Although the D614G mutation enhances the virus’s ability to infect, the serum of the recovered patients can still fight against the mutant virus very well.

Virus variants found in the UK

Increased spread and higher lethality

The latest British report and the mutant virus discovered in the UK not only increased the infectivity of the virus, but also increased the virulence of the virus, which means that this mutant strain is more lethal.

Kitasato said that in January this year, the World Health Organization announced the emergence of a variant of the new coronavirus (mutant strain B.1.1.7) in the UK, which has spread to at least 60 countries around the world.

This mutant strain is mainly the N501Y mutant strain of the virus S protein. N501Y refers to the amino acid at position 501 of S protein changed from aspartic acid (N) to tyrosine (Y). This mutation site is also located in the six key contacts in the cell receptor binding domain (RBD) of S protein One of the residues, this mutation leads to an increase in the binding affinity of the virus S protein to the cell receptor, which in turn enhances the ability of the virus to enter the cell, resulting in a 70% increase in the infectivity of the virus. The S protein of the new British mutant B.1.1.7 contains D614G and N501Y mutations.

There are also South African variants (B.1.351, 501Y.V2) and Brazil variants (B.1.1.248), in addition to D614G, N501Y, E484K variants were also found.

The E484K mutation is also a key contact residue in the receptor binding domain (RBD) of the virus S protein. The E484K mutation of the S protein of the new coronavirus may cause the virus to escape the recognition of the immune system and invalidate the neutralizing antibody.

Source: Xinhua News Agency

Some studies have shown that the virus containing the E484K mutation reduces the neutralizing activity of the neutralizing antibody isolated from the vaccinated human body by more than 10 times. It can be seen that the impact of this mutation on the vaccine is not small, and we need to be very vigilant.

Kitasato said that no E484K mutation was found in the British virus variant. The South African mutant does not exactly match the British mutant, and they were produced independently. The Brazilian virus variant can be said to be almost a variant of the British and South African viruses.

Teenagers become susceptible, don’t let the vaccine go to waste

For viruses that invade the body, the body’s immune system recognizes the S protein of the virus and produces neutralizing antibodies to prevent the S protein from binding to its cell receptor ACE2. Lymphocytes capable of producing neutralizing antibodies will remember the recognition of the virus and provide long-term protection against the virus.

The main purpose of our vaccination is to stimulate our immune system to produce neutralizing antibodies so that we can prevent viruses from invading cells.

Vaccines against viruses are generally vaccinated twice. The first time is to priming the recognition of the virus by the human immune system, and the second time is to enhance or boost the production of neutralizing antibodies of the immune system to promote neutralization of production. Antibody lymphocytes produce memory.

During the two vaccinations, the human immune system will continuously optimize the antibody immune response to the virus, and generate more diverse and stronger neutralizing antibodies.

The rapid spread of the virus in the population will result in the survival of mutant virus strains that can evade the attack of neutralizing antibodies. These virus variants that evade neutralizing antibodies are also mainly concentrated in the field of RBD where the virus S protein binds to cell receptors.

Kitasato said that the mutation of the new coronavirus S protein has led to the expansion of infections worldwide. With the large-scale spread of the mutant virus in the community, children who are relatively unsuitable for infection are also vulnerable to infection, and more than 60% of the infected people, mainly young people, become asymptomatic or mildly infected, which has accelerated the rapid spread of the virus. Difficulties in epidemic prevention and control.

In countries where the epidemic situation is completely out of control such as the United States, India, and Brazil, new and different kinds of variant viruses (variants) will continue to appear.

If these countries that are out of control of the epidemic do not take more active and effective preventive measures for strict control, new virus variants will continue to appear and spread rapidly around the world, leading to the loss of all previous efforts to develop vaccines around the world and more precious lives. The virus swallows.

Therefore, all countries need to strengthen the detection of mutated viruses and make various precautions and preparations. The whole world must unite and work together to win this smoke-free war against the invisible enemy.

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