Today, the leading academic journal Science published a new research paper on the new coronavirus online. A team from the University of Texas at Austin used cryoscope technology to reveal the high-definition structure of the new coronavirus surface S-protein tripolymer.
This information is important for us to understand how new coronaviruses identify and enter cells and how to design effective therapies or vaccines for them.
Two of the study’s co-writers, Daniel Wrapp and Dr. Wang Nianshuang (Photo: Vivian Abagiu/Univ). Of Texas at Austin
S-Protein – The Siege Hammer of the New Coronavirus
If human cells are likened to a solidly guarded city pool, then the S protein is the “siege hammer” of the new coronavirus invading the city pool. Specifically, this is a tripolymer protein, with a large number of glycosylation modifications. Although it looks like a long nail, it “deforms” the receptors on the cell’s surface, combining the virus envelope into the cell membrane, injecting the genetic material inside the virus into the cells and infecting the cells.
The 3D structure scored by the researchers using the frozen mirror technology (Photo: Jason McLellan/Univ). Of Texas at Austin
It is conceivable that if we can see the appearance of this “siege hammer”, we can see the trick, find the weakness, help develop the new coronavirus drugs and vaccines. The cryoscope technology is a tool that allows us to see the structure of proteins.
3D Structure Reveals Mechanism
Based on the first reported sequence of the new coronavirus genome, the researchers expressed the extramyral domain (ectodomain) of the new coronavirus S protein and introduced two proline mutations at the protein C end to stabilize the protein. Previous papers have also shown that such an approach does have a stable effect in similar coronaviruses.
After expressing these prefusion S proteins, the scientists obtained the 3D structure of the S protein using the cryoscope technology, with a resolution of 3.5 E (1 E . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . An analysis of the 3D structure found that its receptor binding domain (RBD) moves up — and when it moves up, the S protein is able to bind to the receptor on the cell surface through this receptor binding domain; It’s a bit like some USB drives we’ve seen in our lives, and you can only get them on the computer when we push the interface out.
The structure of the receptor binding domain facing down (left) and reaching out up (right) (Photo: Resources 1)
The authors say the trait is also present in SARS and MERS viruses, and can be observed in other distant coronaviruses. And when all three receptor binding fields of the S-protein tripolymer are lifted up, and when combined with the receptors on the cell surface, the structure of the entire S protein changes due to instability.
Similarities and similarities with SARS virus S protein
Recently, a number of studies have suggested that the receptors identified by the new coronavirus may be ACE2, as may be the SARS virus. To assess this possibility, the researchers tested the ability of the two viruses to combine with ACE2. Studies have shown that the exoskeleton of the new coronavirus S protein is more affinity with ACE2, which is 10-20 times more binding than the SARS virus’s corresponding S protein region. The authors also note in their paper that this high affinity may be the reason why the new coronavirus is more likely to occur from person to person. But they also stress that this is just speculation. To test the possibility of this speculation, we still need more research.
The new coronavirus S protein has a higher affinity with ACE2, the right picture is a two-dimensional diagram of the negative dye electric mirror, blue is the ACE2 receptor, the S protein tripolymer is labeled in 3 other colors (Photo Source: Resources 1)
It is also because of these similarities with the SARS virus S protein that the researchers further evaluated whether antibodies that bind to the receptor domain of the SARS virus can also bind to the receptor domain of the new coronavirus. However, although the receptor binding domains of the two viruses are very similar, none of the three antibodies tested in the study against SARS viruses were able to bind to the receptor binding domains of the new coronavirus. The researchers note in their paper that while the antibodies they tested represented only a very small number of binding epitopes, the results also suggested that monoclonal antibodies against SARS were not necessarily active against the neocosa. So we still need to develop effective antibodies and other therapies based on the new coronavirus.
There is no doubt that the rapid spread of the new coronavirus outbreak has made the development of vaccines and new drugs urgent. At the end of the paper, the authors point out that a clear structure of s proteins up to the atomic level can better help new drug developers design and screen small molecule drugs, guide vaccine design and antiviral drug development more precisely, and ultimately accelerate the development of appropriate medical instruments.