The spike protein of SARS-CoV-2 can adopt at least 10 structural states in order to cling onto angiotensin-converting enzyme 2 (ACE2) receptor cells in humans, according to a new research.

The research was conducted by Francis Crick Institute, United Kingdom, and was published in the journal Nature.

Researchers believe that their insight will help other scientists and researchers to better understand coronavirus vaccines and treatments.

Mechanism

The outer surface for the coronavirus — spikes — enable the virus to attack ACE2 receptors and proliferate in human cells.

When spikes bind themselves with ACE2 cell surface receptors, the infection begins in the body. This catalyses the release of the virus genome into the cell in subsequent stages. However, the exact nature of the ACE2 binding to the SARS-CoV-2 S protein remains unknown.

Examination

The team of researchers incubated a mixture of the spike protein and ACE2 before trapping different forms of the protein by rapid freezing in liquid ethane.

They examined the samples using cryo-electron microscopy, obtaining tens of thousands of high-resolution images of the different binding stages. They noticed that spikes were present as a mixture of closed and open structures.

Following ACE2 binding at a single open site, the S protein becomes more open, leading to a series of favourable conformational changes, priming it for additional binding, the study noted.

Once the S is bound to ACE2 at all three of its binding sites, its central core becomes exposed, which may help the virus to fuse to the cell membrane, permitting infection, it further added.

Donald Benton, co-lead author and post-doctoral training fellow at the Crick, said in a statement: “By examining the binding event in its entirety, we have been able to characterise S protein structures that are unique to SARS-CoV-2.”

He added: “We can see that as the S protein becomes more open, the stability of the protein will reduce, which may increase the ability of the protein to carry out membrane fusion, allowing infection.”