Structure and binding properties of Pangolin-CoV spike glycoprotein inform the evolution of SARS-CoV-2.

Antoni G Wrobel1 Donald J Benton2 Pengqi Xu3,4 Lesley J Calder5 Annabel Borg6 Chloë Roustan6 Stephen R Martin3 Peter B Rosenthal5 John J Skehel3 Steven J Gamblin7
Affiliations 7 institutions
  1. Structural Biology of Disease Processes Laboratory, Francis Crick Institute, NW1 1AT, London, UK. [email protected].
  2. Structural Biology of Disease Processes Laboratory, Francis Crick Institute, NW1 1AT, London, UK. [email protected].
  3. Structural Biology of Disease Processes Laboratory, Francis Crick Institute, NW1 1AT, London, UK.
  4. Precision Medicine Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China.
  5. Structural Biology of Cells and Viruses Laboratory, Francis Crick Institute, NW1 1AT, London, UK.
  6. Structural Biology Science Technology Platform, Francis Crick Institute, NW1 1AT, London, UK.
  7. Structural Biology of Disease Processes Laboratory, Francis Crick Institute, NW1 1AT, London, UK. [email protected].

Abstract

Coronaviruses of bats and pangolins have been implicated in the origin and evolution of the pandemic SARS-CoV-2. We show that spikes from Guangdong Pangolin-CoVs, closely related to SARS-CoV-2, bind strongly to human and pangolin ACE2 receptors. We also report the cryo-EM structure of a Pangolin-CoV spike protein and show it adopts a fully-closed conformation and that, aside from the Receptor-Binding Domain, it resembles the spike of a bat coronavirus RaTG13 more than that of SARS-CoV-2.

Supporting text Virus Host Location
Evolution, Molecular 176 Angiotensin-Converting Enzyme 2 177 Animals 1948 Binding, Competitive 4 COVID-19 425 Cryoelectron Microscopy 37 Humans 1440 Models, Molecular 99 Pandemics 108 Pangolins 29 Protein Binding 193 Protein Domains 45 SARS-CoV-2 453 Spike Glycoprotein, Coronavirus 274 ACE2 protein, human 87 spike protein, SARS-CoV-2 157

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Functional Mechanism
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