They discover the ‘hidden door’ of SARS-CoV-2 that opens to allow infection

Researchers from UCSD, University of Pittsburgh, University of Texas at Austin, Columbia University and University of Wisconsin-Milwaukee (US) have discovered how glycans, molecules that form a glycolytic residue around the edges of the SARS-CoV-2 protein, Act as gateways for COVID-19 infection.

infection

Thus, this work was published in the journal ‘nature chemistryThe discovery describes the glycan “hidden doors” that were opened to allow entry to SARS-CoV-2. “Essentially, we figured out how the beak actually opens and becomes infected. We uncovered an important secret about the apex on its way to infecting cells. Without this gate, the virus is unable to infect,” explains study leader Romi Amaro.

If the glycan gates can be pharmacologically closed in the closed position, this will effectively prevent the virus from entering and infecting. The glycan coating in the spike protein helps trick the human immune system, as it is nothing more than a sugary residue.

simulation

Supercomputing simulations allowed the researchers to develop dynamic films that revealed glycan gates that activate from one site to another, providing an unprecedented piece of injury history.

“We can really see the opening and closing. That’s one of the coolest things this simulation has to offer: the ability to see very detailed movies. When you see them, you realize you’re seeing something that we could have ignored. If you just look at the closed structure, then you look at the open structure. , it won’t look anything special. Just because we captured the movie of the whole process, you can really see how it works,” Amaro explains.

Their research revealed that the ‘N343’ glycan is the hub that moves the RBD from ‘down’ to ‘up’ to allow access to the ACE2 receptor of the host cell. The researchers describe the activation of the ‘N343’ glycan as a mechanism similar to molecular leveraging.

The researchers created variants of the spike protein and tested to see how glycan portal deficiency affected RBD’s ability to open. The scientists concluded that without this gate, the spike protein RBD could not adopt the shape it needed to infect cells.