Xiaoxiao, a fish and sheep, from the concave temple
Qubit report | public account QbitAI
The new crown virus will undoubtedly be recorded in human history forever.
Today, the number of confirmed cases of the new crown epidemic in the world has exceeded 100 million -approximately 1 in 78 people worldwide is infected.
△ Source: Tencent News
But for this "devil", do you know its true colors?
Now, the 7-person team (Li Sai Lab) from Tsinghua College of Life Sciences, working with the Saudi CV team, has demonstrated the most complete true image of the new crown virus to date .
The 3D, high-definition large image vividly reveals the "look" of the new coronavirus.
The Tsinghua team said that the completion of this work is not for publishing a paper, but only for "scientific evidence to prove the existence of the virus", so that the world can further understand the severity of the new crown epidemic.
What does the 3D new coronavirus look like?
Let's take a look at the overall image of the virus first (all the colors in the picture below do not represent the true colors of the virus, but are only 3D rendering effects):
△ Source: Tsinghua University; see the end of the article for the full video link
From the outside, the virus is like a huge ball with spike protein (red part) distributed on the surface, which can swing freely.
If you dissect the virus partly:
△ Source: Tsinghua University
It can be found that the average diameter of the new coronavirus is about 100nm. Inside the virus, RNA is wrapped around an ordered ribonucleoprotein complex (RNP).
If it is separated layer by layer, the specific components are as follows:
△ Source: Tsinghua University
When the virus enters the human body, the spike protein on its surface can bind to the ACE2 receptor on the surface of the human cell almost instantly, "unlocking" the protection of the cell membrane, and fusing with the cell membrane.
△ Source: Tsinghua University
This rendering is based on the 3D structure of the new crown virus previously analyzed by Li Sai’s laboratory, and the nanographic technology of the King Abdullah University of Science and Technology (KAUST) Ivan Viola team in Saudi Arabia. The scan result of the virus sample is transformed into a 3D visualization image, showing the original shape of the virus:
△ Source: Tsinghua University
But this is not how the virus "will move".
The researchers collected virus data to restore the status of the virus' daily activities.
△ Source: Tsinghua University
After completing the collection of data and the description of the shape of the virus during its activities, the research team submitted these 3D images to Nanographics in Austria to produce the final popular science video.
△ Source: Tsinghua University
The core technology principle behind
How can it be possible to restore the original appearance of the virus so clearly?
Fundamentally, the most important part is to obtain the whole virus 3D structure of the new coronavirus through cryo-electron microscope tomography and electronic tomographic averaging reconstruction technology.
According to the New York Times, in October 2020, this research jointly completed by Li Sai's laboratory and Academician Li Lanjuan was successfully published in "Cell" magazine.
The research results provided the basis for the latest 3D virus popular science image.
For this result, the reviewers praised in the review comments:
"This work shows the most complete image of the new coronavirus I have seen so far. It is also a wonderful application of using cryo-electron microscopy tomography to analyze the complete particle structure."
△ Source: Tsinghua University
Among them, the cryo-electron microscope will use electrons as the "light source" to penetrate the virus sample to obtain structural information inside the virus.
In the laboratory of Tsinghua University, the inactivated new coronavirus was placed under a cryo-electron microscope, and one photo was taken every 3° rotation, a total of 41 photos were taken.
Not only that, but researchers also need to "flash" the virus inside, pass through the envelope, and illuminate the arrangement of ribonucleoprotein complexes inside the virus.
In this research, Li Sai’s team innovatively discovered that the spike protein of the new coronavirus is randomly distributed and flexible, and can swing freely on the surface of the virus like a chain hammer, or even swim.
This is the first time it has been found in enveloped viruses (including smallpox, hepatitis B, hepatitis C, AIDS, rabies, new coronavirus, etc.) .
The swinging characteristics of the spike protein will make the new coronavirus more flexible when attacking cells, and it will help the spike protein to bind to the ACE2 receptor on the cell. This may be one of the reasons for its high infectivity.
Such a complex antigen distribution makes it necessary to consider the specific distribution and structure of the spike protein on the surface of the virus when developing vaccines and neutralizing antibodies.
However, since they are all the same type of virus, why do they need to accurately restore their structure?
In fact, even for enveloped viruses, their overall structure may look very different.
According to an article published by Li Sai in the "Intellectuals", their team had previously conducted special research on enveloped viruses, but from the outside, the structures of these viruses are almost completely different:
△ Source: Li Sai team
Reducing their structures accurately is very important for research on antibodies and corresponding treatments.
Of course, this achievement is also inseparable from the help of Academician Li Lanjuan.
Li Lanjuan’s team is mainly responsible for providing virus strains and screened them specifically for electron microscopy studies.
In addition, Li Lanjuan's team also set up a virus amplification team in response to the special requirements of cryo-electron microscopy experiments, and carried out strict inactivation treatment and inactivation verification on the virus.
Tsinghua Lisai team
Li Sai, the head of the Tsinghua team, is currently a researcher at the School of Life Sciences, Tsinghua University.
He graduated from the Department of Applied Physics of Wuhan University, and then received his master's and doctorate degrees from the Department of Physics, University of Stuttgart, Germany, and the Department of Biophysics, University of Göttingen, Germany.
Before joining the School of Life Sciences of Tsinghua University in 2018, Li Sai worked at the Particle Imaging Center of Oxford University, UK for 5 years.
At present, the main research directions of the Li Sai team are focused on:
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Development of high-resolution cryo-electron microscope tomography
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The assembly of new pathogenic enveloped viruses and the function of the domains disassembled by membrane fusion
According to Google Scholar data, the number of citations of Li Sai's papers is 833, and the h index is 14.
Before unraveling the three-dimensional structure of the new coronavirus, Li Sai had previously worked with colleagues at Oxford University to complete the discovery of the viral structure of enveloped viruses such as Lassa virus, Rift Valley fever virus, and Hantavirus.
From left in the front row: Song Yutong, Li Sai, Zhang Jiaxing
Back row from left: Zhang Zheyuan, Sun Chujie, Chen Yong, Xu Jialu
In cooperation with the team of Li Lanjuan Academician of Zhejiang University, students from Li Sai Lab, Song Yutong, Chen Yong, and Xu Jialu, collaborated with Zhejiang University’s Yao Hangping and Wu Nanping. Sun Chujie, Zhang Jiaxing, and Zhang Zheyuan of the research group also participated in the work.
It is worth mentioning that it has only been more than two years since the establishment of the research group of Researcher Li Sai, and the average age of laboratory members is less than 28 years old.
According to a report from Tsinghua University, most of them faced such a highly contagious virus for the first time in the 100 days of uncovering the true face of the virus, and it was also the first time to tackle such a major and urgent subject.
As a virus researcher, you must have the determination to "sit on a cold bench" during the peaceful period, and the courage to stand up during a major epidemic.
And this time, in cooperation with Nanographics and King Abdullah University of Science and Technology to complete the high-definition science image of the new crown virus, Li Sai admitted:
This is not a result that can be published, but the original intention for us to spend so much time producing these new coronavirus imaging materials is to show the true image of the virus and provide it to the world for free as epidemic prevention and control propaganda and science education materials.
Paper address:
https://www.cell.com/cell/fulltext/S0092-8674(20)31159-4
Video address:
https://www.bilibili.com/video/BV1b54y1p7wg?from=search&seid=12751040449309902573
Reference link:
https://mp.weixin.qq.com/s/q2ZEvzxUweIjJyib6hLGFg
https://view.inews.qq.com/a/WLD20200219026889AC
https://www.delmic.com/zh/techniques/cryogenic-electron-microscopy
https://www.nytimes.com/interactive/2020/health/coronavirus-unveiled.html
http://zhishifenzi.com/depth/depth/10234.html
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