Tracking the opening of spike crowns on the surface of coronaviruses

Circulating over years after the pandemic, SARS-CoV-2 still poses a threat to the human society. The onset of viral infection requires the opening of a trimeric protein, called spike, located on the viral surface essential for binding the host-cell receptors and the subsequent fusion into the host cells. Upon spike-crown opening, one to three Receptor Binding Domains (RBD) rise from the compactly assembled spike head, reaching for the host receptors. Many spike structures were solved that captured RBDs in the different down-to-up trimeric states. These structures not only depict spike’s conformational change but also help design the more efficacious antiviral therapeutics. However, such a dynamic crown-opening pathway is hardly described by only few stationary pictures, and questions yet remain. Do all RBDs rise following the same track in the various studies? If they do, what does this track look like? Is there a common adaptive conformational change of spike as its crown opens? Do all trimeric RBDs rise cooperatively in each spike? And how does it relate to the antibody-binding event? Here, a general RBD-rising pathway, describing the crown-opening dynamics using two angular parameters, was proposed based on analyzing the published spike structures. These analyses describe not only the orientational change of individual RBDs, but also the asymmetric rising preference of the trimeric RBDs in a single-spike entity. In addition, the quantified map clearly describes RBD’s spatial change upon antibody binding, which is often accompanied by an enlarged crown-opening scale. These findings may provide additional clues to develop therapeutics targeting viral spikes in the future.