Written by Kabir Firaque | New Delhi | Updated: July 24, 2020 10:45:13 am Structure of SARS-CoV-2, including the spike protein. (Source: Wikipedia)
The spike protein of SARS-CoV-2 the corona in the coronavirus that causes Covid-19 disease has just revealed new secrets. Researchers have found that the spike protein changes its form after it attaches 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 the knowledge can help in vaccine development.
It is a protein that protrudes from the surface of a coronavirus, like the spikes of a crown or corona hence the name coronavirus. In the SARS-CoV-2 coronavirus, it is the spike protein that initiates the process of infection in a human cell. It attaches itself to a human enzyme, called the ACE2 receptor, before going on to enter the cell and make multiple copies of itself.
Using the technique of cryogenic electron microscopy (cryo-EM), Dr Bing Chen and colleagues at Boston Childrens Hospital have freeze-framed the spike protein in both its shapes before and after fusion with the cell.
The images show a dramatic change to the hairpin shape after the spike protein binds with the ACE2 receptor. In fact, the researchers found that the after shape can also show itself before fusion without the virus binding to a cell at all. The spike can go into its alternative form prematurely.
Dr Chen suggests that assuming the alternative shape may help keep 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 shape may explain this.
More significantly, the researchers speculate that the postfusion form may also protect SARS-CoV-2 from our immune system.
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The postfusion shape could induce antibodies that do not neutralise the virus. In effect, the spikes in this form may act as decoys that distract the immune system.
Antibodies specifically targeting the postfusion state would not be able to block membrane fusion (viral entry) since 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 neutralising epitopes (the part of the virus targeted by antibodies), then the postfusion form too could induce neutralising antibodies, Chen said. But because the two structures are often very different, in particular, in case of SARS-CoV-2 and HIV, I think it is not very likely that the postfusion form would be useful as an immunogen, he explained.
Yes, both the before and after forms have sugar molecules, called glycans, at evenly spaced locations on their surface. Glycans are another feature that helps the virus avoid immune detection.
The researchers believe the findings have implications for vaccine development. Many vaccines that are currently in development use the spike protein to stimulate the immune system. But these may have varying mixes of the prefusion and postfusion forms, Chen said. And that may limit their protective efficacy.
Chen stressed the need for stabilising the spike protein in its prefusion structure in order to block the conformational changes that lead to the postfusion state. If the protein is not stable, antibodies may be induced 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 (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 are not as effective as we all hope.
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Explained: How corona of the virus changes into a hairpin shape and why - The Indian Express
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