Science: Why is the COVID-19 Delta strain so contagious?

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Science: Why is the COVID-19 Delta strain so contagious?

Science: Why is the COVID-19 Delta strain so contagious? The Nobel Prize team reveals the reason behind.

In October 2020, a new variant strain of the new coronavirus, Delta, was discovered in India, and then quickly spread to all parts of the world, becoming the global mainstream new coronavirus strain.

For example, 96% of new cases of COVID-19 infection in the UK are Delta variants. Moreover, the new coronavirus Delta variant is not only extremely contagious, but the infected are more likely to develop severe illness.

So, why has the Delta variant of the new coronavirus suddenly become so powerful?

Recently, a research team led by Professor Jennifer Doudna , a leader in molecular and biology at the University of California, Berkeley, and Nobel Prize winner in chemistry , has conducted research on the modification of virus-like particle (VLP) technology and found that a little-known Delta virus Mutation- R203M mutation can significantly enhance its infectivity.

A live virus study in a biosafety laboratory found that compared with the original COVID-19 pneumonia virus, after the R203M mutation, the lung infectivity was increased 51 times.

One of the authors of this article, Abdullah Syed , a biomedical engineer at the Gladstone Institute of Data Science and Biotechnology, said, “Our research shows that the R203M mutation found in the Delta virus can significantly enhance the ability of the new coronavirus to produce infectious particles. So it will spread faster.

In the future, targeting this mutation may help control the Delta virus infection and help the treatment of patients. “

Science: Why is the COVID-19 Delta strain so contagious?

Related research is titled : Rapid assessment of SARS-CoV-2 evolved variants using virus-like particles , published in the latest issue of Science .

The global COVID-19 situation remains grim

It has been nearly two years since the outbreak of the COVID-19 epidemic in December 2019, but the form of the global COVID-19 epidemic is still not optimistic.

According to the latest statistics of the World Health Organization, as of 17:40 on November 2nd, Central European Time, the number of confirmed COVID-19 cases worldwide increased by 347,703 compared with the previous day, reaching a total of 247 million; the cumulative number of deaths reached 5 million.

Among them, although the United States claims to have the world’s most abundant medical resources and medical care capabilities, and it has stocked a COVID-19 vaccine far exceeding its population, its response to the COVID-19 pneumonia epidemic has been chaotic, and it has become a cumulative number of confirmed cases of COVID-19 pneumonia and a cumulative number of deaths in the world.

The largest number of countries. According to statistics released by Johns Hopkins University in the United States, the United States has a total of 750,000 deaths from COVID-19 pneumonia, accounting for about 15% of the total number of deaths from COVID-19 pneumonia in the world, while the US population accounts for less than 5% of the global population. .

China, which strictly implements the zero-clearing strategy, has recently experienced a gap under the pressure of the spread of the global epidemic and the raging delta virus. The latest round of outbreaks has accumulated more than 700 confirmed cases.

Fortunately, there have been more than 7 billion doses of COVID-19 vaccine worldwide, and half of the population has received at least one dose of the vaccine. Although the global COVID-19 mortality rate will fluctuate greatly with the epidemic situation, it has generally shown a downward trend since January this year.

However, mutant strains of Delta virus have also been discovered recently, and the emergence of an enhanced version of Delta virus has undoubtedly added more uncertainty in the future.

So, why does the Delta virus spread so fast and quickly become the dominant strain of the global COVID-19 pneumonia epidemic?

Improved virus-like particle technology reveals the truth about Delta mutation

Jennifer Doudna , a biology master at the University of California, Berkeley, studied under Thomas Robert Cech, the 1989 Nobel Laureate in Chemistry . She is known as the goddess of CRISPR . He won the Nobel Prize in Chemistry in 2020 for CRISPR technology.

Since live research on the new coronavirus must be carried out in biosafety laboratories of level 3 or above, many scientists do not have such conditions.

Therefore, in order to better study the transmission mechanism of Delta virus, the research team led by Professor Doudna tried to develop a brand-new technology to construct non-infectious virus samples.

We all know that the new coronavirus is a positive-sense single-stranded RNA virus, which cannot reproduce by itself, and can only survive and multiply by “parasitic” on normal human cells.

After the new coronavirus enters the body through the skin and mucous membranes, if it wants to enter the cell, it first needs to use its own spike protein (S protein) to bind to the angiotensin converting enzyme 2 (ACE2) receptor on the cell .

After the two are combined, the cell membrane adsorbs and internalizes the virus, and the virus enters the cytoplasm and unshells and releases the genome. After the genome is released into the cytoplasm, the RNA of the virus will bind to the ribosome of the host cell, begin to translate proteins, and continue to assemble new viruses.

Science: Why is the COVID-19 Delta strain so contagious? Figure | New Coronavirus Delta Variant (Source: Science)

In order to be able to explore the impact of genetic mutations on the spread of the new coronavirus in ordinary laboratories, Professor Doudna and her team modified the traditional virus-like particle technology. The modified structure allows all viral structural proteins to be included, but no genome .

However, in terms of appearance and function, the new coronavirus-like particles are exactly the same as mature new coronaviruses and can invade cells in the laboratory. Due to the stripping of the genome, the virus particles cannot contact the cells to replicate to infect more cells, which means that the virus-like particles cannot spread.

In the process of transforming the virus-like particle technology, Professor Doudna and her team also inserted a piece of mRNA to make it glow when it invaded the cell. The brighter the light, the more mRNA will be released after the invasion.

Next, the researchers began to adjust the protein of the virus-like particles through various mutations, and found that a little-known mutation in the Delta virus, the R203M mutation, can increase the viral mRNA in the infected cell by 10 times.

The R203M mutation mainly changes the nucleocapsid protein of the virus, which is a protein hidden in the virus and used for the packaging of viral genomic RNA. The nucleocapsid protein is a core participant in virus replication, and its role includes stabilizing and releasing viral genetic material.

At the same time, Professor Doudna also found that virus-like particles carrying mutations in the nucleocapsid protein of the new coronavirus Alpha variant and Gamma variant increased their mRNA delivery capacity by 7.5 times and 4.2 times after infecting cells.

This means that the enhanced transmission ability of new coronavirus variants is likely to be related to the mutation of the nucleocapsid protein.

The infectivity of the new coronavirus with the R203M mutation increased by 51 times

Next, Professor Doudna and her team tested a real new coronavirus carrying the R203M mutation in a qualified biosafety laboratory, and found that after invading lung cells in the laboratory, it was compared with the original SARS-CoV -2 strain, the infectivity of the mutant virus has been increased by 51 times.

In the process of new coronavirus infection, the virus produced by one cell will continue to infect another cell. Therefore, if the virus can put its RNA into the host cell more efficiently and produce more viruses, it will obviously be more infectious.

Therefore, the results of this study show that the R203M mutation can make the new coronavirus Delta variant produce more RNA in the cell, assemble more viruses, and make it spread faster.

Currently, researchers are trying to understand how the R203M mutation in the Delta virus and other mutations in the nucleocapsid protein can improve virus particle assembly and host cell RNA delivery. At the same time, they will further investigate whether this process involves host proteins. If so, targeting this target may be an effective way to prevent the spread of Delta virus.

In general, the new virus-like particle system developed by Professor Doudna and his team allows ordinary researchers to effectively study the mechanism of the new coronavirus without a high-level biosafety laboratory. At the same time, they also used this system to find the key factor that greatly improved the transmission ability of the new coronavirus Delta variant.

However, some scholars pointed out that although the new virus-like particle system is powerful, it is still only a model system and cannot fully simulate the actual infection of the virus. Therefore, after using the new virus-like particle system for exploration, it still needs to be further verified in the biosafety laboratory.

Reference:
https://www.science.org/content/article/why-delta-so-infectious-new-lab-tool-spotlights-little-noticed-mutation-speeds-viral-spread

https://www.science.org/doi/10.1126/science.abl6184

Science: Why is the COVID-19 Delta strain so contagious?

(source:internet, reference only)

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