The New Coronavirus will, without a doubt, live on in the annals of human history.
Today, the number of people diagnosed with the global New Coronavirus Epidemic exceeds 100 million – approximately 1 in 78 people worldwide.
Source: Tencent News
But do you know the true nature of this “demon”?
Now, a 7-member team from Tsinghua School of Life Sciences (Li Sai Lab), in collaboration with a Saudi CV team, has presented the most complete real image of the new coronavirus to date.
The 3D, high-definition images reveal the “look” of the new coronavirus in real life.
The Tsinghua team said that the work was done not to publish a paper, but to “prove the scientific argument for the existence of the virus” and to further the world’s understanding of the seriousness of the New coronavirus outbreak.
First, let’s take a look at the overall image of the virus (all colors below do not represent the real color of the virus, but only the 3D rendering).
△Image source: Tsinghua University; see the end of the article for the full video link
From the outside, the virus looks like a huge ball with spiny proteins (red part) on its surface, which can swing freely.
If the virus is partially dissected.
△Image source: Tsinghua University
The average diameter of the new coronavirus is about 100 nm, and inside the virus, the RNA is wrapped around the ribonucleoprotein complex (RNP) in an orderly arrangement.
If the layers are broken down, the specific composition looks like this.
△Image source: Tsinghua University
When the virus enters the human body, the stinger protein on its surface can bind to the ACE2 receptor on the surface of human cells almost instantly, “unlocking” the protection of the cell membrane and thus fusing with it.
Source: Tsinghua University
This effect was achieved by using the 3D structure of the whole virus of the new coronavirus previously resolved by the laboratory of Li Sai, and then using the nanogram technology of Ivan Viola’s team at King Abdullah University of Science and Technology (KAUST) in Saudi Arabia to convert the scans of these virus samples into 3D visual images to show the original shape of the virus.
△Image source: Tsinghua University
But that’s not what the virus looks like when it “moves”.
By collecting virus data, the researchers were able to recreate the daily activities of the virus.
Source: Tsinghua University
After collecting the data and describing the morphology of the virus during its activity, the research team sent the 3D images to Nanographics Austria to make the final science video.
△Image source: Tsinghua University
How is it possible to restore the original appearance of the virus so clearly?
Fundamentally, the most important part is to obtain the full viral 3D structure of the new coronavirus through cryo-electron microscopy tomography, and electron tomography averaging reconstruction techniques.
According to the New York Times, in October 2020, this research, done by the Li Sai laboratory with academician Lanjuan Li, was successfully published in the journal Cell (Cell).
Its research results provided the basis for this latest 3D viral science image.
For this achievement, the reviewers praised in their review comments.
“This work presents the most complete image of a new coronavirus I have seen so far, and it is a wonderful application of using cryoelectron microscopy tomography to resolve the complete particle structure.”
△Image source: Tsinghua University
The cryo-electron microscope will use electrons as the “light source” to penetrate the virus sample to obtain information about the internal structure of the virus.
In Tsinghua University’s lab, inactivated new coronaviruses are placed under the cryo-electron microscope, which takes one picture for every 3° of rotation, for a total of 41 pictures.
In addition, the researchers also needed to “flashlight” the inside of the virus, passing through the capsid to illuminate the structure of the ribonucleoprotein complex inside the virus.
In this study, Li Sai’s team innovatively discovered that the spines of the new coronavirus are randomly distributed and flexible, and can wiggle freely on the surface of the virus like a chain hammer, and even wander around.
This is the first discovery in capsid viruses (including smallpox, hepatitis B, hepatitis C, HIV, rabies, and neocoronavirus).
The oscillating feature of the spinosomal protein would allow the neo-coronavirus to be more flexible in attacking cells and facilitate the binding of the spinosomal protein to the ACE2 receptor on the cell, which may be one of the reasons for its high infectivity.
Such a complex antigenic distribution makes it necessary to consider the specific distribution and structure of the spinosin protein on the viral surface when developing vaccines and neutralizing antibodies.
However, why is it necessary to accurately reduce its structure when it is all the same type of virus?
Indeed, the overall structure of even capsid viruses can look very different.
According to Li Sai’s article in The Intellectual, their team had previously conducted a special study on vesicular membranous viruses, which, however, have almost completely different structures from the outside.
△Image source: Li Sai’s team
The accurate reduction of their structure is very important for the study of antibodies, and corresponding therapies.
This result, of course, could not be achieved without the help of Academician Lanjuan Li.
Lanjuan Li’s team was mainly responsible for providing the viral strains and screening them accordingly, specifically for electron microscopy studies.
In addition, Lanjuan Li’s team also set up an amplification virus team to meet the special requirements of cryo-electron microscopy experiments on samples, and carried out strict inactivation treatment and inactivation verification of the virus.
The leader of this Tsinghua team, Li Sai, is now a researcher in the School of Life Sciences at Tsinghua University.
He graduated from Wuhan University with a bachelor degree in applied physics, and thereafter took his master and PhD degrees from the Department of Physics, University of Stuttgart, Germany, and the Department of Biophysics, University of Göttingen, Germany, respectively.
Prior to joining the School of Life Sciences at Tsinghua University in 2018, Li Sai worked at the Centre for Particle Imaging, University of Oxford, UK for 5 years.
Currently, the main research interests of Sai Li’s team focus on.
High-resolution cryo-electron microscopy tomography method development
Assembly of emerging pathogenic capsid viruses and the function of structural domains de-assembled by membrane fusion
According to Google Scholar data, the citation number of Li Sai’s paper is 833 and the h-index is 14.
Before unraveling the full viral 3D structure of the new coronavirus, Li Sai had previously collaborated with colleagues at Oxford University to complete the viral structure discovery of capsid viruses such as Lassa virus, Rift Valley fever virus, and Hantaan virus.
Front row from left: Yutong Song, Sai Li, Jiaxing Zhang
Back row from left: Zheyuan Zhang, Chujie Sun, Yong Chen, Jialu Xu
In the collaboration with academician Lanjuan Li’s team at Zhejiang University, Yutong Song, Yong Chen and Jialu Xu, students from Li Sai’s lab, are co-author with Hangping Yao and Nanping Wu at Zhejiang University. The group’s Sun Chujie, Zhang Jiaxing and Zhang Zhenyuan also participated in the work.
It is worth mentioning that the group of researcher Li Sai has been established for just over two years, and the average age of the laboratory members is less than 28 years old.
According to Tsinghua University, in the 100 days of uncovering the true face of the virus, most of them are facing such a highly infectious virus for the first Time, and the first time to tackle such a major and urgent topic.
As virus researchers, they must have the determination to “sit on the bench” during times of peace and the courage to step forward during major epidemics.
This time, in collaboration with Nanographics and King Abdullah University of Science and Technology to complete the high-definition scientific images of the new coronavirus, Li Sai admits.
This is not a result that can be published, but the reason we spent so much time to produce these New Coronavirus images is to show the real image of the virus and provide it to the world for free as outbreak prevention and control publicity and science Education materials.
The paper is available at.
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
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