Neglected "glycans" can regulate the spike protein function of COVID-19

If you're an avid reader of science news, you've probably heard of viral proteins like COVID-19 spike protein
.
In the anatomical structure of the virus, what may be less known is a class of molecules
called glycans.
But these are also important
.

Saccharides are complex carbohydrates that adorn the surface of viruses, "each virus has a different distribution of carbohydrates," said
Sriram Neelamegham, an engineering and medical researcher at Buffalo University in New York.
As he explains, HIV uses glycans as shields, using these molecules to dodge antibodies
against viruses.
He added that H1N1 is an influenza virus that uses glycans to enter host cells
.
Now, Neelamegham, along with other scientists, has elucidated the role glycans may play in the function of the SARS-CoV-2 virus that causes COVID-19
.
In a new study, his team analyzed a subset of glycans called N-glycans, focusing on N-glycans
attached to SARS-CoV-2 spike proteins.
The researchers found that several of these N-glycans—especially those that attach to the spike proteins N61 and N801—may be critical
to the function of SARS-CoV-2.
The study was published in Science Advances on September 23,

Neelamegham said: "We found that specific n-glycans appear to regulate the development and functional maturation
of the SARS-CoV-2 spike protein.
This is important because the spike protein is very important
for the virus to enter the host cell.
”

The study used artificial replicants of the SARS-CoV-2 virus known as virus-like particles (VLPs) to some extent
.
The VLPs used in the study were specifically designed to prevent the formation
of various N-glycans on the spike proteins.
In these studies, modifications associated with N61 and N801 reduced the ability of VLPs to enter host cells by about 75-85%, suggesting that these glycans are key weaknesses of the virus, according to the study
.

Neelamegham said that while more research is needed to determine the exact cause of this, N61 and/or N801 may have played a role
in helping to fold the spike protein into the right structure.

To understand the folding mechanism, his team studied the role of various intracellular carbohydrates in combination with "mates" or "lectins" that assist in the synthesis of spikes
.
These studies have shown that a "chaperone" protein called calnexin promotes this type of folding, regulating VLP entry into host cells
.
That's interesting, Neelamegham says, because calnexin is known to bind to N-glycans, although scientists aren't sure if calnexin specifically interacts
with glycans of N61 and N801, as well as other glycans.

The findings highlight that N-stranded glycans on spike proteins may be potential drug targets for COVID-19
.
Neelamegham said the next step in the study is to validate these findings
using appropriate animal models.
The study also highlights the importance of
studying the role of glycans in other diseases caused by viruses.

"Glycomics is a secondary area compared to protein studies: more researchers are focusing on proteins because the primary target of neutralizing antibodies is protein epitopes, but our findings suggest that these glycans are indeed important
in terms of SARS-CoV-2 viral function.
" That's why we chose to go
in that direction.
”