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 |