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

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. It has been suggested that pangolin coronaviruses may be the origin of SARS-CoV-2. Here the authors show that the Pangolin-CoV spike is structurally closely related to the closed form of SARS-CoV-2 spike and exhibits similar binding properties to human and pangolin ACE2; although neither spike binds bat ACE2.

Automated summary

The study suggests that coronaviruses from bats and pangolins may be implicated in the origin and evolution of SARS-CoV-2, with spikes from a pangolin coronavirus closely related to SARS-CoV-2 showing strong binding to human and pangolin ACE2 receptors. The structural and binding similarities between the pangolin coronavirus spike and the closed form of SARS-CoV-2 spike indicate a potential connection between the two viruses.