Updated: July 24, 2020 6:59:49 am
Structure of SARS-CoV-2, including spike protein. (Source: Wikipedia)
The SARS-CoV-2 spike protein, the ‘crown’ in the coronavirus that causes Covid-19 disease, has just revealed new secrets. Researchers have discovered that the spike protein changes its shape after attaching itself to a human cell, folding in on itself and assuming a rigid hairpin shape. The researchers have published their findings in the journal Science, and believe that the knowledge may aid in vaccine development.
What is spike protein?
It is a protein that protrudes from the surface of a coronavirus, like the peaks of a crown or crown, hence the name ‘coronavirus’. In the SARS-CoV-2 coronavirus, it is the spike protein that initiates the infection process in a human cell. It binds to a human enzyme, called the ACE2 receptor, before entering the cell and making multiple copies of itself.
What has the new research found?
Using the cryogenic electron microscopy (cryo-EM) technique, Dr. Bing Chen and colleagues at Boston Children’s Hospital have frozen the spike protein in both forms, before and after fusion with the cell.
Cryo-EM images of SARS-CoV-2 before and after fusion with the human cell. The post-fusion shape is like a stiff fork. (Source: Provided by Dr. Bing, Chen, Boston Children’s Hospital)
The images show a dramatic change in hairpin shape after the spike protein binds to the ACE2 receptor. In fact, the researchers found that the “after” shape can also show up before fusion, without the virus attaching to a cell. The beak may enter its alternate form prematurely.
What does that mean?
Dr. Chen suggests that taking the alternate form can help prevent SARS-CoV-2 from breaking down. Studies have shown that the virus remains viable on various surfaces for various periods of time. Chen suggests that the rigid form can explain this.
More significantly, the researchers speculate that the post-fusion form may also protect SARS-CoV-2 from our immune system.
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How can you protect the virus from the immune system?
The post-fusion form could induce antibodies that do not neutralize the virus. Indeed, spikes in this form can act as decoys that distract the immune system.
“Antibodies that specifically target the post-fusion state could not block membrane fusion (viral entry) as it would be too late in the process. This is well established in the field of other viruses, such as HIV, “Chen told The Indian Express, by email.
In principle, if both conformations shared neutralizing epitopes (the part of the virus directed by the antibodies), then the post-fusion form could also induce neutralizing antibodies, Chen said. “But because the two structures are often very different, particularly in the case of SARS-CoV-2 and HIV, I think the post-fusion form is not very likely to be useful as an immunogen,” he explained.
Do the two forms share some similarity?
Yes, both the “before” and “after” forms have sugar molecules, called glycans, in evenly spaced places on their surface. Glycans are another feature that helps the virus avoid immune detection.
How is knowledge about the alternative form useful?
The researchers believe the findings have implications for vaccine development. Many vaccines currently in development use the spike protein to stimulate the immune system. But these can have different mixtures of the prefusion and post-fusion forms, Chen said. And that can limit its protective efficacy.
Chen emphasized the need to stabilize the spike protein in its prefusion structure to block the conformational changes that lead to the post-fusion state. If the protein is not stable, antibodies can be raised, but they will be less effective in terms of blocking the virus, he said.
“Using our prefusion structure as a guide, we should be able to do better (by introducing stabilizing mutations) to mimic the prefusion state, which could be more effective in eliciting neutralizing antibody responses,” Chen told The Indian Express. “We are in the process of doing this in case the first round of vaccines is not as effective as we all hope.”
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