Mechanisms of Coronavirus Cell Entry Mediated by the Viral Spike Protein

By S. Belouzard, J. Millet, Beth. N. Licitra, Gary R. Whittaker. Viruses, 2012

1,279 citations recorded by the source corpus.

Coronaviruses are enveloped positive-stranded RNA viruses that replicate in the cytoplasm. To deliver their nucleocapsid into the host cell, they rely on the fusion of their envelope with the host cell membrane. The spike glycoprotein (S) mediates virus entry and is a primary determinant of cell tropism and pathogenesis. It is classified as a class I fusion protein, and is responsible for binding to the receptor on the host cell as well as mediating the fusion of host and viral membranes—A process driven by major conformational changes of the S protein. This review discusses coronavirus entry mechanisms focusing on the different triggers used by coronaviruses to initiate the conformational change of the S protein: receptor binding, low pH exposure and proteolytic activation. We also highlight commonalities between coronavirus S proteins and other class I viral fusion proteins, as well as distinctive features that confer distinct tropism, pathogenicity and host interspecies transmission characteristics to coronaviruses.

Subfields: Animal Science and Zoology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/55ef87ca0d0cdad3973a94294211e8e9ea8bcc87

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Animal Science and Zoology

1. Fang Li
2. Gary R. Whittaker
3. J. Millet
4. J. Shang
5. Yushun Wan

In Infectious Diseases

1. Fang Li
2. J. Millet
3. Gary R. Whittaker
4. J. Shang
5. Yushun Wan
6. Q. Geng
7. W. Hagen
8. D. Veesler

Citations in the corpus

• In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges (2020, background): “Although not necessary for infection, furin cleavage of S is linked to virulence in vivo (Li 2016; Belouzard et al., 2012).”
• The Molecular Docking Study of Potential Drug Candidates Showing Anti-COVID-19 Activity by Exploring of Therapeutic Targets of SARS-CoV-2 (2020, background): “The association of S proteins gives the virion a trimeric form, which gives it a crown-like structure and the name coronavirus.[22] The S protein has a role in viral entry.”
• Cell entry mechanisms of SARS-CoV-2 (2020, background): “Moreover, to fuse membranes, SARS-CoV spike needs to be proteolytically activated at the S1/S2 boundary, such that S1 dissociates and S2 undergoes a dramatic structural change (22, 23).”
• Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein (2014, background): “The coronavirus spike (S) is unusual in that a range of different proteases can cleave and activate it (10).”
• Structure, Function, and Evolution of Coronavirus Spike Proteins (2016, background): “Thus, proteolysis of coronavirus spikes can lead directly to membrane fusion and thereby serves as an essential trigger for membrane fusion (111, 112).”
• COVID-19 pathophysiology: A review (2020, neutral): “The coronavirus spike is unusual among viruses because a range of different proteases can cleave and activate it [38].”