Functional and genetic analysis of viral receptor ACE2 orthologs reveals a broad potential host range of SARS-CoV-2.

Proceedings of the National Academy of Sciences of the United States of America
Yinghui LiuQiang Ding

Abstract

The pandemic of COVID-19, caused by SARS-CoV-2, is a major global health threat. Epidemiological studies suggest that bats (Rhinolophus affinis) are the natural zoonotic reservoir for SARS-CoV-2. However, the host range of SARS-CoV-2 and intermediate hosts that facilitate its transmission to humans remain unknown. The interaction of coronavirus with its host receptor is a key genetic determinant of host range and cross-species transmission. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as the receptor to enter host cells in a species-dependent manner. In this study, we characterized the ability of ACE2 from diverse species to support viral entry. By analyzing the conservation of five residues in two virus-binding hotspots of ACE2 (hotspot 31Lys and hotspot 353Lys), we predicted 80 ACE2 proteins from mammals that could potentially mediate SARS-CoV-2 entry. We chose 48 ACE2 orthologs among them for functional analysis, and showed that 44 of these orthologs-including domestic animals, pets, livestock, and animals commonly found in zoos and aquaria-could bind the SARS-CoV-2 spike protein and support viral entry. In contrast, New World monkey ACE2 orthologs could not bind the SARS-CoV-2 spike protein and support viral entry...Continue Reading

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Citations

Apr 10, 2021·One Health Outlook·R J DelahayC Gortazar
May 1, 2021·Viruses·Su Datt LamChristine Orengo
Jun 11, 2021·Journal of Veterinary Diagnostic Investigation : Official Publication of the American Association of Veterinary Laboratory Diagnosticians, Inc·Hugh Y Cai, Allison Cai
Jun 20, 2021·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Lijing ZhangXingliang Zhang
Jun 13, 2021·Virus Research·Iryna V GoraichukAnton P Gerilovych
Aug 8, 2021·Animals : an Open Access Journal From MDPI·Kimberly EkstrandKathleen N Morgan
Aug 8, 2021·Animals : an Open Access Journal From MDPI·Sebastian Giraldo-RamirezJulian Ruiz-Saenz
Aug 28, 2021·International Journal of Molecular Sciences·Sachiko KoyamaThomas Heinbockel

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