How the viral “corona” transforms into a hairpin shape, and why

Structure of SARS-CoV-2 containing spike proteins. (Source: Wikipedia)

SARS-CoV-2 Spike Protein—“Corona” Coronavirus Because of that COVID-19 Illness-A new secret is revealed. Researchers have found that the spike protein changes shape after it attaches to human cells and folds into a stiff hairpin shape. Researchers publish their findings in the journal Science and believe their knowledge will help vaccine development.

What is a spike protein?

It is a protein that sticks out of the surface of a coronavirus, like a crown or a corona spike, and hence the name “coronavirus”. In the SARS-CoV-2 coronavirus, it is the spike proteins that initiate the infection process in human cells. It attaches to a human enzyme called the ACE2 receptor, then enters the cell and makes multiple copies of itself.

What did the new study find?

Using cryo-electron microscopy (cryo-EM), Dr. Bing Chen and colleagues at Boston Children’s Hospital freeze-framed spike proteins of both shapes before and after fusion with cells.

Low-temperature EM images of SARS-CoV-2 before and after fusion with human cells. The shape after fusion is like a stiff hairpin. (Source: Dr Bing, Chen, Boston Children’s Hospital)

The image shows a dramatic change in hairpin shape after the spike protein binds to the ACE2 receptor. In fact, researchers have discovered that the “after” shape also appears before fusion, even though the virus is not bound to the cell at all. Spikes could prematurely replace it.

What does that mean?

Dr. Cheng suggests that assuming a different shape may help prevent the destruction of SARS-CoV-2. Studies show that viruses can survive on different surfaces for different periods of time. Chen suggests a rigid shape may explain this.

More importantly, researchers speculate that post-transfusion forms may also protect SARS-CoV-2 from the immune system.

How can I protect the virus from the immune system?

The post-fusion shape can elicit antibodies that do not neutralize the virus. In fact, this form of spike can act as a decoy that disrupts the immune system.

“Antibodies specifically targeting the post-fusion state are too slow a process to block membrane fusion (virus entry). It is well established in other viral areas such as HIV. Indian Express, on mail.

In principle, post-fusion forms may also induce neutralizing antibodies if both conformations share a neutralizing epitope (the part of the virus that the antibody targets), says Chen. “But the two structures are often very different, and I think the post-fusion form is unlikely to be useful as an immunogen, especially for SARS-CoV-2 and HIV,” he explained.

Are there any similarities between the two forms?

Yes, both “before” and “after” forms have sugar molecules called glycans evenly spaced on the surface. Glycans are another feature that helps viruses bypass immune detection.

How can knowledge of alternative shapes help?

Researchers believe this finding will impact vaccine development. Many vaccines currently in development use spike proteins to stimulate the immune system. However, these may have various combinations of pre- and post-fusion morphologies, Chen said. And that may limit their protective effect.

Chen emphasized the need to stabilize the spike protein in its pre-fusion structure in order to block the conformational changes that lead to its post-fusion state. If the proteins are not stable, antibodies can be induced, but they are less effective in blocking the virus, he said.

“Using our prefusion structure as a guide should allow for better (introducing stabilizing mutations) to mimic the prefusion state, which is more effective at inducing neutralizing antibody responses. It’s possible,” Chen told Indian Express. “We do this in case the first round of vaccines is not as effective as we all expect.”

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