SARS-CoV-2 Structural Binding Mechanisms Revealed

According to a new study, the spike protein on the surface of the SARS-CoV-2 Coronavirus can adopt at least ten distinct structural states when in contact with the human virus receptor ACE2. The research team from the Francis Crick Institute published their study today in Nature. 

In order to understand the binding mechanisms between ACE2 and the virus, the team worked with a mixture of the spike protein and ACE2. They examined these samples using cryo-electron microscopy, obtaining high-resolution images of the different binding stages.

They observed that the spike protein exists as a mixture of closed and open structures. Following ACE2 binding at a single open site, the spike protein becomes more open, leading to a series of favorable conformational changes, priming it for additional binding. Once the spike 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.

"By examining the binding event in its entirety, we've been able to characterize spike structures that are unique to SARS-CoV-2," says Donald Benton, co-lead author. The team hopes these findings will help with more targeted development of new treatments and vaccines.