Variation in structural motifs within SARS-related coronavirus spike proteins

• Published in: PLoS pathogens 2024-05, Vol.20 (5), p.e1012158
• Main Authors: Hills, Francesca R, Eruera, Alice-Roza, Hodgkinson-Bean, James, Jorge, Fátima, Easingwood, Richard, Brown, Simon H J, Bouwer, James C, Li, Yi-Ping, Burga, Laura N, Bostina, Mihnea
• Format: Article
• Language: English
• Subjects: ACE inhibitors; ACE2; Amino Acid Motifs; Amino acids; Analysis; Angiotensin; Angiotensin-converting enzyme 2; Animal human relations; Animals; Betacoronavirus; Biliverdin; Binding; Binding Sites; Biology and life sciences; Chiroptera - virology; Composition; Coronaviridae; Coronaviruses; COVID-19; COVID-19 - virology; Cryoelectron Microscopy; Density; Disease transmission; Dosage and administration; Electron microscopy; Fatty acids; Glycan; Glycoproteins; Health aspects; Humans; Interfaces; Linoleic acid; Medicine and health sciences; Models, Molecular; Pandemics; Peptidyl-dipeptidase A; Protein Binding; Proteins; Receptors; Research and Analysis Methods; SARS-CoV-2 - chemistry; Severe acute respiratory syndrome coronavirus 2; Severe acute respiratory syndrome-related coronavirus - chemistry; Severe acute respiratory syndrome-related coronavirus - genetics; Severe acute respiratory syndrome-related coronavirus - metabolism; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - metabolism; Spike protein; Unsaturated fatty acids; Viral diseases; Water chemistry; Zoonoses
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1012158

SARS-CoV-2 is the third known coronavirus (CoV) that has crossed the animal-human barrier in the last two decades. However, little structural information exists related to the close genetic species within the SARS-related coronaviruses. Here, we present three novel SARS-related CoV spike protein structures solved by single particle cryo-electron microscopy analysis derived from bat (bat SL-CoV WIV1) and civet (cCoV-SZ3, cCoV-007) hosts. We report complex glycan trees that decorate the glycoproteins and density for water molecules which facilitated modeling of the water molecule coordination networks within structurally important regions. We note structural conservation of the fatty acid binding pocket and presence of a linoleic acid molecule which are associated with stabilization of the receptor binding domains in the "down" conformation. Additionally, the N-terminal biliverdin binding pocket is occupied by a density in all the structures. Finally, we analyzed structural differences in a loop of the receptor binding motif between coronaviruses known to infect humans and the animal coronaviruses described in this study, which regulate binding to the human angiotensin converting enzyme 2 receptor. This study offers a structural framework to evaluate the close relatives of SARS-CoV-2, the ability to inform pandemic prevention, and aid in the development of pan-neutralizing treatments.