Madrid, 19 ago. (European Press) –
Researchers at UCSD, University of Pittsburgh, University of Texas at Austin, Columbia University and University of Wisconsin-Milwaukee (US) have discovered how glycan molecules form a sugary residue around SARS. -CoV-2 protein edges, serving as gateways for COVID-19 infection.
Thus, this work, published in the journal Nature Chemistry, describes the discovery of glycan “hidden doors” that open to allow entry to SARS-CoV-2. “Essentially, we figured out how the beak actually opens and becomes infected. We’ve uncovered an important secret about the beak on its way to infecting cells. Without this gate, the virus is essentially 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.
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 were able to really see the opening and closing. And that’s one of the most interesting things that this simulation has to offer: the ability to see very detailed movies. When you watch them, you realize that you’re seeing something we would otherwise have ignored. If you just look at the closed structure, then You looked at the open structure, it wouldn’t look anything special. Just because we filmed the whole process, you 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 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.