Structural basis for human coronavirus attachment to sialic acid receptors

Tortorici, M. Alejandra; Walls, Alexandra C.; Lang, Yifei; Wang, Chunyan; Li, Zeshi; Koerhuis, Danielle; Boons, Geert-Jan; Bosch, Berend-Jan; Rey, Félix A.; de Groot, Raoul J.; Veesler, David

Coronaviruses cause respiratory tract infections in humans and outbreaks of deadly pneumonia worldwide. Infections are initiated by the transmembrane spike (S) glycoprotein, which binds to host receptors and fuses the viral and cellular membranes. To understand the molecular basis of coronavirus attachment to oligosaccharide receptors, we determined cryo-EM structures of coronavirus OC43 S glycoprotein trimer in isolation and in complex with a 9-O-acetylated sialic acid. We demonstrate that the ligand binds with fast kinetics to a surface-exposed groove and interactions at the identified site are essential for S-mediated viral entry into host cells, but free monosaccharide did not trigger fusogenic conformational changes. The receptor-interacting site is conserved in all coronavirus S glycoproteins that engage 9-O-acetyl-sialogycans, with an architecture similar to the ligand-binding pockets of coronavirus hemagglutinin esterases and influenza virus C/D hemagglutinin-esterase-fusion glycoproteins. Our results demonstrate these viruses evolved similar strategies to engage sialoglycans at the surface of target cells.