Architects of infection: A structural overview of SARS-related coronavirus spike glycoproteins
Francesca R. Hills, Jemma L. Geoghegan, Mihnea Bostina
Abstract
The frequency of zoonotic viral emergence within the Coronaviridae family highlights the critical need to understand the structural features of spike proteins that govern viral entry and host adaptation. Investigating the structural conservation and variation in key regions of the spike protein—those involved in host range, binding affinity, viral entry, and immune evasion—is essential for predicting the evolutionary pathways of coronaviruses, assessing the risk of future host-jumping events, and discovering pan-neutralising antibodies. Here we summarise our current structural understanding of the spike proteins similar to SARS-CoV-2 from the Coronaviridae family and compare key functional similarities and differences. Our aim is to demonstrate the significant structural and sequence conservation between spike proteins from a range of host species and to outline the importance of animal coronavirus surveillance and structural investigation in our endeavour for pandemic preparedness against emerging viruses. • Overall structural comparison of spike glycoproteins similar to SARS-CoV-2 reveals high levels of structural conservation and outlines potential host-jumping pathways. • Many solved spike proteins can perform in vivo human ACE2 binding and pseudovirus entry, which is increased up to ∼200-fold with single RBD mutations. • Sequence and structure variation exists in S proteins similar to SARS-CoV-2 to preferentially adopt the RBD ‘down’ conformation, favourable for bat coronavirus transmission routes.