Cross-species recognition of squirrel ACE2 by the receptor binding domains of SARS-CoV-2, RaTG13, PCoV-GD and PCoV-GX.

Publication date: Jul 22, 2025

SARS-CoV-2 has a broad animal host range, but its origin and intermediate hosts are still debated. Arctic ground squirrel is proved to be a susceptible animal host of SARS-CoV-2 and RaTG13, as the Arctic ground squirrel ACE2 (sACE2) could bind to the RBDs of SARS-CoV-2 and RaTG13, and support transduction of the SARS-CoV-2 and RaTG13 pseudovirions. Here, we determined crystal structures of sACE2 bound to the RBDs of RaTG13, PCoV-GD, PCoV-GX, SARS-CoV-2 A372T and SARS-CoV-2 JN. 1 variant. SPR assay indicated that RBD residues 493, 498 and 501 might be important for sACE2 recognition. Notably, N322-linked glycans of sACE2 were found to be in contact with S375 of the RaTG13 RBD. Moreover, the recent SARS-CoV-2 KP. 2 and KP. 3 variant RBDs could also bind to the sACE2. Our results provide further insights into interactions between coronavirus RBD and cell receptor ACE2, which may promote our understanding of SARS-CoV-2 evolution.

Concepts Keywords
Arctic coronavirus RBDs
Coronavirus crystal structures
Host SARS-CoV-2 evolution
Squirrel SARS-CoV-2 variants

Semantics

Type Source Name
disease IDO host
disease IDO assay
disease IDO cell

Original Article

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