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Topic selection of COVID-19's thesis
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The top academic journal Cell published an important paper about COVID-19 online yesterday in the form of "advance publication". A large-scale multinational team "searched one by one" in the vast database, and found three cell types that were most likely to be directly attacked by COVID-19, and also found another tricky point of its invasion of human cells.

The authors of the study said that sharing these data and findings as soon as possible will help to focus on clarifying the role of COVID-19 in the human body and "find out why some people are more susceptible to infection and how to find the best treatment".

Vulnerable cells

Two months ago, the academic team of Jingwei reported that COVID-19 needed two keys to invade cells-ACE2 receptor used by viruses to bind and TMPRSS2 protease to help viruses invade. However, it has not been clarified which cell will express these two protein. In order to find these cells, researchers from nearly 50 different institutions around the world, led by scientists from Massachusetts Institute of Technology and Boston Children's Hospital, have conducted large-scale screening work in the past two months, only to find those cells that are most likely to infect COVID-19.

Wuxi pharmatech content team mapping

The research team used "single cell RNA sequencing technology" to answer this question. This technology can know which genes will be activated in each specific cell type. As long as the cells express ACE2 and TMPRSS2 at the same time, the risk of COVID-19 infection is very high.

The results showed that less than 10% of human respiratory cells and intestinal cells produced ACE2 and TMPRSS2 simultaneously. These cells are divided into three types: the first is the cup-shaped secretory cells in the nasal cavity, whose usual function is to secrete nasal mucus; The second type is lung type II alveolar cells, which are responsible for maintaining alveolar function. The third kind of cell is very interesting. They come from the digestive tract rather than the respiratory tract. They are called absorptive intestinal epithelial cells. As the name implies, it is located in the small intestine and is responsible for the absorption of nutrients.

This discovery is of great significance for all kinds of research that need cell experiments to screen drugs. "Many existing respiratory cell lines may not contain all cell types, and may omit relevant cells." Dr. Jose Ordovas-Montanes, one of the leaders of this study, pointed out: "Using more accurate cell models, we can be more targeted in drug screening and provide a more solid foundation for subsequent experiments in mice and non-human primates."

▲ The results of sampling in macaques show that the susceptible cell pattern is similar to that of humans.

Interferon: beneficial or harmful?

Originally, this work has been done here, which is already very meaningful. But after determining the types of susceptible cells, scientists asked, how do these cells work?

This makes the researchers unexpectedly discover a phenomenon that may be of great significance in the treatment of COVID-19's disease-after the epithelial cells are stimulated by interferon, the gene encoding ACE2 will be enhanced! Interferon is a cytokine secreted by human immune system after detecting virus, which usually plays an important role in defending virus. However, interferon up-regulates ACE2, which means that there are more "gates" on the cell surface for COVID-19 to enter.

▲ Research schematic diagram

"ACE2 plays an important protective role in various lung injuries," explained Dr. Ordovas-Montanes. "When ACE2 increases, it is usually a protective response. However, since COVID-19 is targeting ACE2, we suspect that COVID-19 used a normal protective response. "

To give a more vivid example, at present, doctors also use interferon to fight against viral infection when treating patients with COVID-19's disease. However, this discovery means that this treatment may actually make patients express more ACE2, so that more cells may be infected by COVID-19. Whether the advantages of using interferon outweigh the disadvantages or the disadvantages outweigh the advantages needs further weighing.

postscript

At the end of the abstract, scientists also described to us the potential cunning side of COVID-19: when infected with the virus, the interferon reaction in our body may drive the production of a large number of ACE2. Under normal circumstances, ACE2 can protect the lungs. However, the presence of these protein will be used by COVID-19 as a springboard for them to invade more cells. This may explain why some patients get worse after using interferon.

We can also see from the list of research authors of this paper that during the difficult period of the epidemic, there are still many scientists involved in this work, including many researchers from Boston, which is one of the areas where the COVID-19 epidemic is quite serious in the United States. "This is an incredible collective effort to share data not only in Boston, but also with partners around the world in order to provide relevant information as soon as possible." Another person in charge, Dr. Alex K. Dr. Shalek, said, "When all people unite to solve a difficult problem, the result is encouraging."

More about Cell: COVID-19's ability to break through the human defense line is really too strong. Please continue to pay attention to the column of deep space science and technology information, and deep space Bian Xiao will continue to update you with more science and technology news.

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