This article comes from WeChat public account: qubit (ID: QbitAI) , author: Guo Yipu, dry out, the original title:” the new crown virus has been “stripped off a layer of skin”! West Lake University successfully analyzes the spatial structure of viral cell receptors, helping to develop specific drugs

After the new crown virus invaded many human bodies, a structure called ACE2 suddenly became popular in the academic circle.

As a structure that already exists in human body cells, ACE2 has been blamed:

It’s you spy who brought the new crown virus into human cells!

Although ACE2 itself is the normal structure of human cells, how can it be “utilized” by the new crown virus?

Aiming at the “easy use” of ACE2, what drugs and treatments should be provided to save more people?

First of all, we must find out the details of ACE2 and understand its structure, so that we can prescribe the right medicine.

Now, West Lake University has done it.

ACE2: Cell door handle “abducted” by the new crown virus

Today’s (February 19) At 3 am, the research team of West Lake University launched the latest research results on the pre-printed platform bioRxiv: using freezing Electron microscopy was used to successfully analyze the full-length structure of ACE2.

This is the first time that the full length structure of ACE2 has been successfully analyzed in the world.

What’s the use? Research and development of anti-epidemic drugs has greatly helped.

ACE2, full name Angiotensin-converting enzyme 2, Chinese name angiotensin converting enzyme 2 .

The main physiological role is to promote the maturation of angiotensin (a peptide hormone that controls vasoconstriction and blood pressure) The kidneys and intestines are widespread.

Only, when the virus invaded, ACE2 was “abducted” by the virus.

It is the receptor for SARS coronavirus (SARS-CoV) and human coronavirus NL63, which can be said to be the majority of coronaviruses invading the human body The essential.

For example, when it is “abducted” by the SARS coronavirus, it will look like this, like a big lobster:

The part of the “lobster tongs” is the S protein of the SARS virus, which is tightly combined with the PD part of ACE2. In this way, ACE2 is forced to become an “innervation” and introduce the virus into cells.

Recently, the research team of the University of Texas at Austin also successfully analyzed the structure of the S protein of the new crown virus and pointed out that the affinity between ACE2 and the RBD of the new crown virus is higher than that of the RBD of the SARS virus by 10- 20 times.

In other words, In contrast to SARS, the new crown virus is more handy in “kidnapping ACE2”.

Although it is not yet possible to directly draw the conclusion that “New crown virus is 10-20 times more infectious than SARS”, a comparison of “affinity” also counts as strong infectivity of new crown virus, and found a scientific basis.

The research team of West Lake University said: “In the process of SARS virus and ‘new crown virus’ invading the human body, ACE2 is like a ‘door handle’ , and the virus opens it into the cells Door. “

The analysis of the full-length structure of ACE2 will undoubtedly provide important structural biological data support for the subsequent research and development of vaccines and antiviral drugs.

“It will help to understand the structural basis and functional characteristics of coronavirus entry into target cells, and will play an important role in discovering and optimizing inhibitors that block entry into cells”, explained Professor Zhang Linqi, Director of the Global Health and Infectious Disease Research Center of Tsinghua University .

In addition, Weibo netizen “Three Rice Bags” also gave a more vivid metaphor: “Just know what the keyhole looks like and then use this key. Otherwise, you can use countless keys to try which one is OK. Open the door. “

The world’s first full-length structure of ACE2 was resolved

According to the information released by West Lake University, the full picture of ACE2 looks like this:

The blue and off-white parts above are the two structures of ACE2 PD (peptidase domains) and CLD (Collectrin-like domain) , but ACE2 is difficult to obtain stably in vitro, often with an intestinal amino acid transporter B 0 AT1 appears together.

The research team of West Lake University gave a bold hypothesis: This complex is very likely to stabilize ACE2, and through co-expression, it can obtain a high-quality and stable complex, which constitutes the X shape above.

After confirming this special existence form of ACE2, its three-dimensional structure was analyzed under cryo-electron microscopy:

The resolution in the picture is 2.9 Angstroms. “Angle” (Symbol Å) is a unit for measuring the length of light waves and the diameter of a molecule. An Angstrom is 0.1 nm.

The structure of ACE2 looks like this:

As can be seen from these picture materials, ACE2 exists in the form of dimer and has both open and closed conformational changes , but the two conformations Each contains a mutual recognition interface with a corona virus .

Of course, ACE2 is only a part of the process in which neocoronavirus infects human cells. The key lies in the combination of the S protein of ACE2 with ACE2 protein .

Understanding the structure of the novel coronavirus S protein and its interaction with ACE2 are important directions for further research.

The team at West Lake University said that the findings provide a basis for further analysis of the three-dimensional structure of the full-length ACE2 and S-protein complexes of the new crown virus.

In their opinion, the work itself provides a lot of interesting clues for understanding the infection of cells by the new crown virus. For example:

Can the dimer of ACE2 and the trimer of neocrown virus S protein occur higher-level cross-linking , thereby promoting the fusion or endocytosis of the virus with the host cell membrane?

Previous studies have shown that if the extracellular region of ACE2 is cut, it will promote coronavirus more effectivelyInfection, but the complex structure of ACE2 and B 0 AT1 showed that the presence of B 0 AT1 may prevent the protease from approaching this cleavage site. Does this explain: Symptoms of virus infection mainly occur in the lungs without B 0 AT1?


Team Achievement of West Lake University


This paper has a total of five authors, the first author and the corresponding author, all from the Key Laboratory of Structural Biology Research of Zhejiang Province at West Lake University. Shi Yigong, the founder of West Lake University, served as the director. Professor Yan Ning has a great origin-it is well known that President Shi Yigong of the West Lake University and Professor Yan Ning are well-known teachers and disciples in the science class.

In this study, the first author is Yan Renhong (left in the figure below) , a postdoctoral fellow at School of Life Sciences, West Lake University. He studied at Shandong University with a bachelor’s degree.

After graduation, I will go to West Lake University for postdoctoral research. (Professor Yan Ning revealed that after graduating from his doctorate, he didn’t want to go abroad because he didn’t want to have a different relationship.)

The corresponding author is Zhou Qiang. (above right) , Qiqihar, Heilongjiang. Year 2000