Structural basis for human coronavirus attachment to sialic acid receptors

By M. A. Tortorici, A. Walls, Yifei Lang, Chunyan Wang, Zeshi Li, Danielle Koerhuis, G. Boons, B. Bosch, F. Rey, R. Groot and 1 more. 2019

541 citations recorded by the source corpus.

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 show that the ligand binds with fast kinetics to a surface-exposed groove and that interactions at the identified site are essential for S-mediated viral entry into host cells, but free monosaccharide does 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 those of 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. Structural and functional analyses reveal how 9-O-acetyl sialic acid is recognized by the human coronavirus OC43 S glycoprotein and how this interaction promotes viral entry.

Subfields: Ecology, Infectious Diseases

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Citations in the corpus

SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2 (2020, background): “acetylneuraminic acid (Hulswit et al., 2019; Tortorici et al., 2019), middle east respiratory syndrome virus (MERS) binds 5-N-acetyl-neuraminic acid (Park et al.”
Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein (2020, methodology): “As is the case for other b-coronavirus S glycoproteins, including SARS-CoV S (Gui et al., 2017; Kirchdoerfer et al., 2018; Pallesen et al., 2017; Park et al., 2019; Song et al., 2018; Tortorici et al., 2019;Walls et al., 2016a;Walls et al., 2016b;Walls et al., 2019; Yuan et al., 2017), the S1 subuni”
The human coronavirus HCoV-229E S-protein structure and receptor binding (2019, background): “The S-protein is a trimer in both the pre-fusion and post-fusion 63 conformations and cryo-EM analysis has provided structures for both conformations (20-30).”
Controlling the SARS-CoV-2 spike glycoprotein conformation (2020, unknown): “It was previously noted that the RBD up states observed in MERS and SARS-CoV-1 were not observed in the OC43, MHV, or HKU1 S-protein structures 10 .”
Structural insights into coronavirus entry (2019, background): “Free 9-O-Ac-Sia, however, did not trigger S conformational changes associated with membrane fusion (Tortorici et al., 2019).”
Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies (2020, unknown): “The S proteins were modified as previously described (Li et al., 2019; Tortorici et al., 2019; Walls et al., 2020).”
SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2 (2020, unknown): “Mapping the binding site for sialic acids in other coronavirus S proteins has proved elusive, but modeling studies suggest a location distinct from the HS-binding site shown in Figure 1 (Park et al., 2019; Tortorici et al., 2019).”