COVID-19: How coronavirus changes shape in human body and decoys immunity

The protein spike could assume its alternative form prematurely.

Coronavirus research: The spike protein of the COVID-19-causing SARS-CoV-2, which forms the ‘corona’ of the coronavirus, has been found to change its form once it attaches itself to the human cell. Researchers have found that once the coronavirus binds itself to the human cell with the help of these spike proteins, the proteins fold in on themselves to take a rigid hairpin shape, a report in IE stated. The research has been published in Science journal, and the authors hope the knowledge would aid in the development of vaccines against the virus.

Coronavirus: Spike protein explained

According to the IE report, spike protein is a protein protruding from the coronavirus’ surface, much like the spikes on a crown or corona, which is why the virus is called coronavirus. In SARS-CoV-2, the coronavirus which causes COVID-19, the spike protein is the part that begins the infection process in a human cell, by attaching itself to an enzyme called ACE2 receptor. It then enters the cell, where it proceeds to replicate itself.

Coronavirus spike proteins: Findings of the new research

The research was carried out by Dr Bing Chen and his colleagues at the Boston Children’s Hospital using the cryogenic electron microscopy (cryo-EM) technique. With this, the researchers freeze-framed the spike protein in both of its shape before and after its fusion with the human cell. The images, according to the report, showed the massive changes to the hairpin shape of the protein after they attach themselves to the ACE2 receptor. The report stated that researchers also found that the “after” shape of the protein could also become visible before the fusion, without the virus attaching itself to the human cell at all. The protein spike could assume its alternative form prematurely, the report added.

Significance of this research

According to the report, Dr Chen has suggested that this alternative shape might be preventing SARS-CoV-2 from breaking down. Earlier studies have found that the virus can remain viable on several surfaces for varying time periods, which according to Chen, might be explained due to the rigid shape.

More importantly, the post-fusion form of the virus might be protecting it from the human immune system, the researchers have speculated.

How does this shape affect human immunity to the virus?

According to the IE report, the hairpin shape of the virus could lead to the release of antibodies that do not neutralize the coronavirus, essentially acting as decoys to distract the human immune system.

The report quoted Dr Chen as saying that the antibodies which specifically target the post-fusion state of the virus, would not have the ability to block the membrane fusion or the entry of the virus since it would be very late in the process. He further said that this was well established in cases of other viruses, like HIV.

He added that if both the conformations shared the part of the virus which the antibodies targeted, or the neutralising epitopes, then the post-fusion form could also induce neutralising antibodies. However, since the two structures are often different, especially when it came to SARS-CoV-2 and HIV, he said it was not highly likely that the post-fusion form of the virus would help as an immunogen.

Similarities in the two forms

The report added that both the forms of the virus had sugar molecules known as glycans and they were located at evenly spaced places on the virus’ surface. Glycans also aid the virus in avoiding immune detection, the report stated.

How is the knowledge about the alternative shape useful?

Researchers are of the view that these findings can help in the development of vaccines. Several vaccines currently being developed stimulate the human immune system using the spike protein, the report said. However, these may be varied combinations of the pre-fusion and post-fusion states of the virus, Dr Chen said, adding that this may limit the protective efficacy of the vaccines.

The report further cited Dr Chen as saying that there is a need to stabilise the spike protein in its pre-fusion state so that conformational changes that lead to the post-fusion state could be blocked. He was further cited as saying that in case the protein is not stabilised, the induced antibodies would be less effective in blocking the virus.