Architecture of the SARS coronavirus prefusion spike

Beniac, Daniel R.; Andonov, Anton; Grudeski, Elsie; Booth, Tim F.

doi:10.1038/nsmb1123

Cited by 290 publications

(273 citation statements)

References 14 publications

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“…The two domains, NTD and RBD, of the S1 region that CoV use for attachment to cell surface molecules (Fig. 1) docked into the cryo-electron microscopy map (gray) of the trimeric SARS-CoV S (EMD-1423) (Beniac et al, 2006). Ribbon representations of the SARS-CoV RBD (yellow) and the MHV NTD (blue) alone or bound to ACE2 (Fig.…”

Section: Discussionmentioning

confidence: 99%

A structural view of coronavirus–receptor interactions

et al. 2014

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In the coronavirus (CoV), the envelope spike (S) glycoprotein is responsible for CoV cell entry and host-to-host transmission. The S is a multifunctional glycoprotein that mediates both attachment of CoV particles to cell surface receptor molecules as well as membrane penetration by fusion. Receptor-binding domains (RBD) have been identified in the S of diverse CoV; they usually contain antigenic determinants targeted by antibodies that neutralize CoV infections. To penetrate host cells, the CoV can use various cell surface molecules, although they preferentially bind to ectoenzymes. Several crystal structures have determined the folding of CoV RBD and the mode by which they recognize cell entry receptors. Here we review the CoV-receptor complex structures reported to date, and highlight the distinct receptor recognition modes, common features, and key determinants of the binding specificity. Structural studies have established the basis for understanding receptor recognition diversity in CoV, its evolution and the adaptation of this virus family to different hosts. CoV responsible for recent outbreaks have extraordinary potential for cross-species transmission; their RBD bear large platforms specialized in recognition of receptors from different species, which facilitates host-to-host circulation and adaptation to man.

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Section: Discussionmentioning

confidence: 99%

A structural view of coronavirus–receptor interactions

et al. 2014

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“…Palmitoylation of cysteine residues within the endodomain was found to be important for regulating fusogenicity of S (Petit et al, 2007; Shulla and Gallagher, 2009). Cryo-EM studies on single particles of the SARS-CoV have shed light on the overall architecture of S protein trimers and the conformational changes they undergo during fusion (Beniac et al, 2006; Beniac et al, 2007). While individual structures of key domains of S, such as the receptor binding domain (Li et al, 2005a; Peng et al, 2011; Wu et al, 2009) or the six-helix bundle (Xu et al, 2004), have been extensively studied, it is important to note that, to date, a complete crystal structure determination of the S ectodomain for any coronavirus is still lacking.…”

Section: Coronavirus S Proteinmentioning

confidence: 99%

Host cell proteases: Critical determinants of coronavirus tropism and pathogenesis

2015

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Coronaviruses are a large group of enveloped, single-stranded positive-sense RNA viruses that infect a wide range of avian and mammalian species, including humans. The emergence of deadly human coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV) have bolstered research in these viral and often zoonotic pathogens. While coronavirus cell and tissue tropism, host range, and pathogenesis are initially controlled by interactions between the spike envelope glycoprotein and host cell receptor, it is becoming increasingly apparent that proteolytic activation of spike by host cell proteases also plays a critical role. Coronavirus spike proteins are the main determinant of entry as they possess both receptor binding and fusion functions. Whereas binding to the host cell receptor is an essential first step in establishing infection, the proteolytic activation step is often critical for the fusion function of spike, as it allows for controlled release of the fusion peptide into target cellular membranes. Coronaviruses have evolved multiple strategies for proteolytic activation of spike, and a large number of host proteases have been shown to proteolytically process the spike protein. These include, but are not limited to, endosomal cathepsins, cell surface transmembrane protease/serine (TMPRSS) proteases, furin, and trypsin. This review focuses on the diversity of strategies coronaviruses have evolved to proteolytically activate their fusion protein during spike protein biosynthesis and the critical entry step of their life cycle, and highlights important findings on how proteolytic activation of coronavirus spike influences tissue and cell tropism, host range and pathogenicity.

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“…The peplomer includes a globular portion and a protein stalk. By adopting the helical structure that is characteristic of class I virus fusion proteins, the protein stalk connects the globular portion to the transmembrane domain [17]. The Nterminal S1 domain constitutes the globular region, and the stalk is made up of the membrane-proximal S2 domain.…”

Section: The Role Of the Spike Protein Of Tgev And Pedvmentioning

confidence: 99%

Three Main Inducers of Alphacoronavirus Infection of Enterocytes: Sialic Acid, Proteases, and Low pH

et al. 2018

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Transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV) are similar coronaviruses, causing diseases characterized by vomiting, diarrhea, and death from severe dehydration in piglets. Thus, they have caused huge losses to the swine-breeding industry worldwide. Nowadays, they are easily transmitted among the continents via vehicles, equipment, and cargo. Both viruses establish an infection in porcine enterocytes in the small intestine, and their spike (S) proteins play a key role in the virus-cell binding process under unfavorable conditions when the intestine with a low pH is filled with a thick layer of mucus and proteases. Sialic acid, proteases, and low pH are three main inducers of coronavirus infection. However, the details of how sialic acid and low pH affect virus binding to the host cell are not determined, and the functions of the proteases are unknown. This review emphasizes the role of three factors in the invasion of TGEV and PEDV into porcine enterocytes and offers more insights into Alphacoronavirus infection in the intestinal environment.

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Architecture of the SARS coronavirus prefusion spike

Cited by 290 publications

References 14 publications

A structural view of coronavirus–receptor interactions

A structural view of coronavirus–receptor interactions

Host cell proteases: Critical determinants of coronavirus tropism and pathogenesis

Three Main Inducers of Alphacoronavirus Infection of Enterocytes: Sialic Acid, Proteases, and Low pH

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