Cetacean coronavirus spikes highlight S glycoprotein structural plasticity

Area of Science:

• Structural biology
• Virology
• Molecular evolution

Background:

• Coronaviruses (CoVs) can infect new hosts, but spike (S) proteins of gamma- and deltacoronaviruses are less understood than alpha- and betacoronaviruses.
• Research has primarily focused on zoonotic CoVs, leaving avian-infecting gamma- and deltacoronaviruses understudied.

Purpose of the Study:

• To elucidate the high-resolution structures of S proteins from gammacoronaviruses infecting marine mammals.
• To investigate the unique quaternary architecture, novel domains, and glycosylation patterns of these CoV spike proteins.

Main Methods:

• High-resolution cryo-electron microscopy (cryo-EM) for structural determination.
• Sequence identity analysis to compare viral strains.
• Glycoproteomic analyses to characterize glycosylation.

Main Results:

• Revealed unique quaternary architecture of gammacoronavirus S proteins, distinct from other CoVs.
• Identified a novel, tripodal quaternary assembly of the S1 subunit with shielded receptor-binding sites.
• Discovered an additional N-terminal domain (S10) with cupin superfamily structural similarity, representing exaptation.
• Demonstrated extensive N- and O-glycosylation, forming a dense glycan shield potentially masking epitopes.

Conclusions:

• Gammacoronavirus S proteins exhibit significant structural diversity, including alternative assemblies and novel domains.
• Extensive glycosylation plays a crucial role in shielding the S protein and potentially facilitating host jump.
• These findings offer insights into coronavirus adaptability and host range expansion mechanisms.