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

Antoni G Wrobel,Steven J Gamblin,Peter B Rosenthal,Lesley J Calder,Annabel Borg,Donald J Benton,Stephen R Martin,Chloë Roustan,John J Skehel,Pengqi Xu

doi:10.1038/s41467-021-21006-9

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.

Highlights

Coronaviruses of bats and pangolins have been implicated in the origin and evolution of the pandemic SARS-CoV-2
A similar pattern of binding was observed for SARS-CoV-2 S (Fig. 1B); preferred and strong binding to human ACE2, weaker binding to pangolin ACE2 and very weak binding to bat ACE2
The binding of pangolin S to human and pangolin ACE2 is comparable to SARS-CoV-2 S (Table 1 and Supplementary Fig. 1E), in keeping with the very high sequence and structural similarity between their two RBDs (Table 2)

Summary

Introduction

Coronaviruses of bats and pangolins have been implicated in the origin and evolution of the pandemic SARS-CoV-2. Others have suggested[5] and we recently demonstrated[6], that the bat coronavirus RaTG13, the closest known relative of SARSCoV-2, is unlikely to be able to infect human cells because of the very low affinity of its spike protein (S) for the human receptor. For this reason, it has been speculated that SARS-CoV-2 could have reached the human population via an intermediate host[5]. We analyse ACE2-binding properties and the structure of S protein from a Pangolin-CoV closely related to SARS-CoV-28,9

Methods

Results

Conclusion