Cryo-EM structures of HKU2 and SADS-CoV spike glycoproteins provide insights into coronavirus evolution

Porcine coronavirus SADS-CoV has been identified from suckling piglets with severe diarrhea in southern China in 2017. The SADS-CoV genome shares similar to 95% identity to that of bat alpha-coronavirus HKU2, suggesting that SADS-CoV may have emerged from a natural reservoir in bats. Here we report the cryo-EM structures of HKU2 and SADS-CoV spike (S) glycoprotein trimers at 2.38 angstrom and 2.83 angstrom resolution, respectively. We systematically compare the domains of HKU2 spike with those of alpha-, beta-, gamma-, and delta-coronavirus spikes, showing that the S1 subunit N- and C-terminal domains of HKU2/SADS-CoV are ancestral domains in the evolution of coronavirus spike proteins. The connecting region after the fusion peptide in the S2 subunit of HKU2/SADS-CoV adopts a unique conformation. These results structurally demonstrate a close evolutionary relationship between HKU2/SADS-CoV and beta-coronavirus spikes and provide insights into the evolution and cross-species transmission of coronaviruses. Several coronaviruses infecting humans and animals have emerged in recent years. Here, the authors provide structures of the spike proteins of the porcine coronavirus SADS-CoV and closely related bat coronavirus HKU2, providing insights into evolution of coronavirus spike proteins.