open access

https://hdl.handle.net/2115/98142

Molecular and Functional Characterization of Sika Deer ACE2 as a Receptor for SARS-CoV-2

英語

wildlife

2025-09-30

John Wiley & Sons

Microbiology and immunology

Surveillance of SARS-CoV-2 in white-tailed deer (WTD, Odocoileus virginianus) has revealed its widespread and sustained transmission across North America, with evidence suggesting possible transmission from deer to humans. In the following surveillance studies in other deer species, however, little evidence of infection spread was found, including in sika deer (Cervus nippon) in our previous study. Differences in the structure of the virus entry receptor angiotensin-converting enzyme 2 (ACE2) are known to act as one of the functional barriers to SARS-CoV-2 infection. To investigate the molecular basis of the lack of SARS-CoV-2 transmission to sika deer, we performed structural and functional analyses of the sika deer ACE2 in comparison with WTD ACE2. Comparison of sika deer ACE2 sequence and those of cervid species with WTD ACE2, followed by in silico molecular dynamics analysis, revealed a substitution of lysine to asparagine in position 31 commonly found in cervid ACE2s can potentially alter binding to the SARS-CoV-2 spike (S) protein receptor-binding domain (RBD). Functional assays in cells expressing sika deer and WTD ACE2s showed minimal differences in viral binding and replication, demonstrating that SARS-CoV-2 can similarly utilize ACE2 from both species. These findings suggest that sika deer and possibly other cervids may be highly susceptible to SARS-CoV-2 and highlight the need to investigate other factors impacting virus spread in deer populations.

学術雑誌論文

Accepted Manuscript

This is the peer reviewed version of the following article: Kovba, A., Igarashi, M., Mizuma, K., Ohari, Y., Onuma, M., Shimozuru, M., Shimizu, K., Yamanaka, M., Matsuno, K. and Tsubota, T. (2025), Molecular and Functional Characterization of Sika Deer ACE2 as a Receptor for SARS-CoV-2. Microbiology and Immunology, 69: 533-543. https://doi.org/10.1111/1348-0421.70012, which has been published in final form at https://doi.org/10.1111/1348-0421.70012. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.

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