Why the dissemination of COVID-19 Delta variant was so strong?

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Why the dissemination of COVID-19 Delta variant was so strong?

Chinese scientists have found out the reason for the strong dissemination of “Delta”!

Although the Omicron mutant strain has arrived, the Delta mutant strain is still the dominant strain globally. It took only a few months from the first discovery to the raging fire that swept the world.

Why does the delta mutant spread so fast? What makes Delta mutants have super fast spreading power?

After more than three months of “chasing the culprit”, the research team including Professor Huang Bo and Professor Qin Chuan from the Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences finally found out how the Delta mutant strain achieved ultra-fast transmission.

Related research results were published online in the international academic journal “Signal Transduction and Targeted Therapy”.

“We found that the delta mutant strain can break through the defense mechanism of anti-inflammatory alveolar macrophages.

By increasing the number of amino groups, it completes the protonation of spike proteins and activates cathepsin under a relatively high pH environment.

The protease cuts the viral spike protein, causing the membrane of the virus particle and the membrane of the endocytic body to split at the contact site, allowing the viral RNA to be released into the cytoplasm, thereby realizing the rapid spread of the virus.” Huang Bo told on December 21 Journalist of Science and Technology Daily.

Due to its high viral load, strong transmission capacity, and rapid spread, the delta mutant strain of the COVID-19 virus quickly raged around the world after its emergence and became the main strain of the COVID-19 pneumonia epidemic.

“How Delta mutants with T478K, P681R, and L452R mutations achieve ultra-fast transmission, we didn’t know before. This study uncovered the mystery of the ultra-fast transmission of Delta mutants.” Huang Bo said.

If you want to understand the transmission mechanism of the delta mutant, you have to start with how the new coronavirus infects people.

The respiratory airways of the human lungs swell at the end, forming balloon-like structures called alveoli. The alveoli are the place where oxygen and carbon dioxide exchange.

There is a thin layer of liquid on their surface to maintain the expansion of the alveoli and prevent them from collapsing. When the human body inhales air, it not only inhales oxygen into the alveoli, but also inevitably inhales the potential bacteria and viruses in the air into the alveoli.

In order to prevent the invasion of this pathogen, immune cells, especially macrophages with phagocytic function, settle in the liquid layer on the surface of the alveoli, which account for more than 95% of the immune cells that settle in the liquid layer, which is called medically. Alveolar macrophages. These macrophages can swallow the particles and microorganisms contained in the inhaled air, keeping the alveoli clean.

Therefore, once the new coronavirus enters the alveoli, the alveolar macrophages will immediately engulf the virus particles to form vesicles that wrap the virus particles in the cell membrane, that is, endosomes, and then fuse with the lysosomes in the cytoplasm, thereby phagocytosing the phagocytic organisms. The body including the virus is completely degraded.

However, the new coronavirus can use the specific state of alveolar macrophages to escape from the endocytic corpuscles, and in turn use the macrophages to reproduce themselves.

In this regard, Huang Bo explained that this is because the cathepsin that depends on the low pH value in the endocytic body is activated.

The cathepsin cuts the viral spike protein, causing the membrane of the virus particle and the membrane of the endocytic body to crack at the contact site. Open, allowing viral RNA to be released into the cytoplasm.

In this way, the new coronavirus can achieve rapid proliferation.

Alveolar macrophages will be polarized in both the pro-inflammatory and anti-inflammatory directions.

The pH of pro-inflammatory endosomes is acidic and can promote cathepsin activation, while the pH of anti-inflammatory endocytic bodies is alkaline and can Inhibit cathepsin activation.

“A small number of people whose alveolar macrophages tend to be pro-inflammatory, are susceptible to being infected by the new coronavirus and are prone to develop severe illness.

However, the alveolar macrophages of normal people tend to be anti-inflammatory, which can usually inhibit cathepsin activation and thus can It is better to resist the invasion of the new coronavirus, showing no disease or mild infection.” Huang Bo pointed out.

However, research by Huang Bo and others found that the Delta mutant strain can break through the defense mechanism of anti-inflammatory alveolar macrophages.

“The delta mutant strain is mainly due to changes in multiple amino acids of its spike protein, the rule of change is the addition of amino groups. Cathepsin activity is closely related to the pH of the endocytic corpuscle.” Huang Bo said, low pH.

It can activate cathepsin. The essence of this process is that the amino group of the viral spike protein is more likely to get protons, that is, the amino group is protonated.

By increasing the number of amino groups, the delta mutant can complete spike protein protonation at a relatively high pH, which can be cleaved by cathepsin, allowing viral RNA to be released and rapid spread.

Huang Bo said that this research will help to provide targets for the development of small molecule drugs, acting on alveolar macrophages, blocking the escape of delta mutant virus RNA from endosomes, and then delivering the virus to the lysosome completely.

Degradation to achieve the effect of prevention and early infection control of the virus.