Variation in structural motifs within SARS-related coronavirus spike proteins.

Autor: 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
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Zdroj: PLoS Pathogens; 5/28/2024, Vol. 20 Issue 5, p1-19, 19p
Abstrakt: 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. Author summary: SARS-related coronaviruses pose a significant threat to human health and prosperity by virtue of their pandemic potential. Transmission of SARS-related coronaviruses from animals to humans risks another pandemic like the recent COVID-19, MERS or SARS pandemics. To better understand the risk these viruses pose to humans, SARS-related coronaviruses from animal origin should be structurally studied to assess key features related to pathogenicity and stability. The spike proteins from two civet coronaviruses (cCoV-007 and cCoV-SZ3) and a horseshoe bat coronavirus (bCoV-WIV1) were structurally resolved by cryo-electron microscopy and analysed for similarity to SARS-CoV-2, the causative agent of COVID-19, for which bats and civets have both been implicated as potential hosts. The quality of the reconstructions allowed us to determine important features of the spikes, such as the network of water molecules that coordinate and stabilize the fatty acid in the fatty acid binding pocket, which are typically not visible in glycoprotein reconstructions. We also identified a different conformation of a key loop in the receptor binding domain of these spikes. This loop has previously been identified as being involved in host recognition and binding. This study offers a structural insight into spike protein structural features which promote success in coronaviruses that infect bats and civets, and helps us to better understand what drives the success of these viruses in such a broad host range. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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