Tongji team further reveals the mechanism of new Coronavirus infection with alveoli

Not long ago, scientists from the Pasteur Institute in Shanghai, Chinese Academy of Sciences, and the Wuhan Institute of Viruses of the Chinese Academy of Sciences have found that the entry of the new coronavirus (2019-nCoV) into cells requires the presence of angiotensin-transformation enzyme 2 (ACE2). These two studies support ACE2 as a drug target to treat patients with new coronavirus infection in Wuhan.

Therefore, it is necessary to have an in-depth understanding of the distribution of ACE2 in various tissues and cells in the human body, which is important for the development of appropriate drug treatment.

Recently, a team of professors from Tongji University School of Medicine in Shanghai, published an important research result on bioRxiv, a preprinted website.

Tongji team further reveals the mechanism of new coronary viral infection with alveoli

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They analyzed single-cell RNA sequencing data from more than 43,000 human lung cells (non-new coronavirus infections) and found that more than 80 percent of ACE2 in the lungs was distributed on the surface of type II alveolar epithelial cells (AT2).

To their surprise, these AT2 cells not only express ACE2, which binds to the new coronavirus, but also have dozens of high gene expressions that are closely related to viral replication and transmission. You know, Professor Zuo analyzed data on non-infected people, which means that AT2 cells are the ideal target for the new coronavirus in Wuhan.

In addition, they found that men appeared to have a higher percentage of cells expressing ACE2 than women, and that Asians were likely to have a higher percentage of ACE2 cells than other species.

Zhao Yu and Zhao Zixian are the co-authors of the research paper.

Tongji team further reveals the mechanism of new coronary viral infection with alveoli

Prediction model of the combination of new coronavirus S-protein and human ACE2 in Wuhan

As we already know last week, the free energy of The S-protein and ACE2 of human cells identified by the new coronavirus in Wuhan is lower than SARS, but the binding ability is still very strong, far higher than the minimum value required for viral binding.

In addition, cell experiments have also been confirmed, ACE2 is necessary for Wuhan new coronavirus into cells, basically can confirm that ACE2 is the receptor of Wuhan new coronavirus.

The previous study is very important because the expression and distribution of receptors determine the path of viral infection, and understanding the infection pathway of the virus is important for understanding the pathogenesis and designing treatment strategies.

Tongji team further reveals the mechanism of new coronary viral infection with alveoli

The true face of Wuhan’s new coronary virus (electron microscope photo)

as we know, the lungs are very complex organs with many different types of cells. Previous immunohistalogical studies have analyzed the expression of ACE2 in human lung tissue, and the results show that ACE2 is expressed in a variety of cells such as type I alveoli, type II alveoli, bronchial epithelial and vascular endothelial. However, the method used before has some problems in specificity and other aspects, and is not accurate enough in quantitative terms.

Therefore, Professor Zuo’s team believes that a more accurate analysis of the expression of ACE2 is necessary. This time they used single-cell RNA sequencing techniques.

Instead of analyzing rna data from lung cells in people with the new coronary virus in Wuhan, however, they used an open-source database. The database contains data on single-cell RNA sequencing of lung cells in eight healthy lung transplant donors, including a total of 43,134 cells.

Tongji team further reveals the mechanism of new coronary viral infection with alveoli

Basic situation of 8 donors

Overall, about 0.64% of human lung cells express ACE2, and 83% of ACE2 expression cells are type II alveoli epithelial cells (AT2), which account for about 1.4% of all AT2 cells. AT1 cells, gas lothes, fibroblasts, endothelial cells, and macrophages also express ACE2, but the proportion is very low and the human body is very different.

So is there any other characteristic of the cells that express ACE2?

Further analysis surprised the researchers.

Comparing ace2 with type II alveoli epithelial cells that express ACE2, the researchers found that there were significantly higher levels of expression of dozens of genes in those type II alveoli epithelial cells that expressed ACE2, which related to virus replication, assembly, and life cycle regulation.

Researchers believe the new coronavirus in Wuhan appears to have evolved into a virus capable of hijacking type II alveoli epithelial cells to help it reproduce and spread itself.

The researchers then further analyzed the relationship between the expression of ACE2 and other formures.

They found no association between the number of cells expressing ACE2 and age or smoking status (the one that says smoking prevents viral infections can stop). And men appearto edgtosof ACE2 to be higher (1.66 percent vs 0.44 percent). It seems to suggest that men are more susceptible to the virus than women.

The results are also highly consistent with early epidemiological data. Early infection data published in the top academic journal, The Lancet, by Professor Huang Zhaolin of Wuhan Jinyintan Hospital show that there are 30 infections among men and 11 among women.

Tongji team further reveals the mechanism of new coronary viral infection with alveoli

Photo: pixabay

In addition, they found that Asian men had a higher percentage of ACE2 cells than others (2.5 percent vs 0.47 percent). The researchers believe this may explain why SARS and the new coronavirus are spreading in Asia.

Overall, Professor Zuo’s team explored the expression of ACE2 in human lung cells at single-cell resolution, and found that ace2 was expressed mainly in type II alveoli epithelial cells, and that this cell population had many high gene expressions that were conducive to viral reproduction and transmission. This partly explains why patients develop severe alveoli damage after infection.

However, the study involved a small number of human samples and did not in-depth study at the protein level, so the above conclusions need to be further validated by further clinical studies.

The good news is that on the 25th of this month, Wang Yuedan and the team of ChuMing of Peking University’s School of Basic Medicine, after learning that ACE2 is a possible receptor, screened more than 4,100 drugs on the market using an artificial intelligence drug screening system and found that commonly used drugs such as Mushutan may be targeted at ACE2 therapeutic drugs.

In addition, it is reported that Shenzhen has launched AIDS drugs for the treatment of new pneumonia clinical research.

In any case, it is hoped that scientists and doctors will make early and substantial progress in the treatment of the new coronavirus infection.