Key result
Cryo-EM reveals FIPV-1146 spike protein transitions to a standing conformation to bind cat aminopeptidase N.
Why the study?
FIPV-II infects felids using cat aminopeptidase N as its cell-entry receptor, but the molecular details remain unclear.
The study provides structural insights into the entry mechanism and zoonotic constraints of FIPV-II, identifying key residues for receptor binding and cross-species tropism.
Structures of FIPV-II spike inform feline receptor use; leaves open zoonotic risk for related human coronaviruses.
Type-II feline infectious peritonitis virus (FIPV-II) is a lethal alphacoronavirus, whose high homology with the human coronavirus CCoV-HuPn-2018 carries the risk of potential zoonotic FIPV-II transmission to humans. FIPV-II infects felids using cat aminopeptidase N (cAPN) as its cell-entry receptor, but the molecular details remain unclear. Here, we resolved cryo-electron microscopy (cryo-EM) structures of the spike (S) trimer of a representative FIPV-II strain 79-1146 (FIPV-1146), and of its complex with cAPN. The reconstructions reveal structural transitions of the S protein between the “standing” and “lying” receptor-binding domain (RBD) conformation upon complex formation with cAPN in its open conformation. Structural and mutational analyses revealed that the cAPN residues R378, D751 and R779, as well as the N748-linked glycan are essential for high-affinity RBD engagement. Cross-species analysis demonstrated narrow tropism of FIPV-1146, limited to felids and canids. Introducing the N595K and Q596R substitutions found in transmissible gastroenteritis virus (TGEV) into the FIPV-1146 RBD expands its binding capacity to APNs from pig, bovine, horse and giant panda. These findings provide insights into the entry mechanism and zoonotic constraints of FIPV-II, with potential relevance for antiviral strategies against coronaviruses.
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Niu et al. (2026) studied Feline infectious peritonitis. Cryo-EM and mutational analysis was evaluated on Cryo-EM structure resolution and receptor binding affinity. Cryo-EM structures revealed that FIPV-1146 spike protein transitions to a standing conformation to bind cat aminopeptidase N, and specific mutations expand its receptor binding to other species.
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