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Publication Abstract from PubMed

Coronaviruses have caused a number of major epidemics in humans and animals, including the current pandemic of COVID-19 that has brought renewed focus on evolution and interspecies transmission of coronaviruses. Swine acute diarrhea syndrome coronavirus (SADS-CoV), which was recently identified in piglets in southern China, is an alphacoronavirus that originates from the same genus of horseshoe bats as Severe Acute Respiratory Syndrome CoV (SARS-CoV), and was reported to be capable of infecting cells from broad range of species, suggesting a considerable potential for interspecies transmission. Given the importance of coronavirus spike glycoprotein (S) in host range determination and viral entry, we report a cryo-EM structure of the SADS-CoV S-trimer in prefusion conformation at 3.55 A resolution. Our structure reveals that SADS-CoV S-trimer assumes an intra-subunit quaternary packing mode in which the S1-NTD and S1-CTD of the same protomer pack together by facing each other in the "lying-down" state. SADS-CoV S has several distinctive structural features that may facilitate immune escape, such as relatively compact architecture of the S-trimer and epitope masking by glycan shielding. Comparison of SADS-CoV S with those of the other coronavirus spike proteins suggested that the structural features of SADS-CoV S are evolutionarily related to other genera rather than being that of a typical alphacoronavirus. These data provide new insights into the evolutionary relationship between spike glycoproteins of SADS-CoV and other coronaviruses and extends our understanding of their structural and functional diversity.SIGNIFICANCE In this article, we report the atomic-resolution pre-fusion structure of spike protein from swine acute diarrhea syndrome coronavirus (SADS-CoV). SADS-CoV is a pathogenic alphacoronavirus responsible for large-scale outbreak of fatal disease in pigs that was reported to be capable of interspecies transmission. We describe the overall structure of the SADS-CoV spike protein and conduct detailed analysis of its main structural elements. Our results and analyses are consistent with the previous phylogenetic studies and suggest that SADS-CoV spike protein is evolutionarily related to spike proteins of betacoronaviruses, with strong similarity in S1-NTDs and marked divergence in S1-CTDs. Moreover, we discussed possible immune evasion strategies used by SADS-CoV spike protein. Our study provides insights into structure and immune evasion strategies of SADS-CoV spike protein and broadens the understanding of evolutionary relationships between coronavirus spike proteins of different genera.

Cryo-electron microscopy structure of the SADS-CoV spike glycoprotein provides insights into an evolution of unique coronavirus spike proteins.,Guan H, Wang Y, Perculija V, Saeed AFUH, Liu Y, Li J, Jan SS, Li Y, Zhu P, Ouyang S J Virol. 2020 Aug 19. pii: JVI.01301-20. doi: 10.1128/JVI.01301-20. PMID:32817223^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.