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

• DOI: 10.1073/pnas.2025373118
• Publication Date: 2021-03-03T20:25:15Z
• Authors: Yinghui Liu; Gaowei Hu; Yuyan Wang; Wenlin Ren; Xiaomin Zhao; Fansen Ji; Yunkai Zhu; Fei Feng; Mingli Gong; Xiaohui Ju; Yuanfei Zhu; Xia Cai; Jun Lan; Jianying Guo; Min Xie; Lin Dong; Zihui Zhu; Jie Na; Jianping Wu; Xun Lan; Youhua Xie; Xinquan Wang; Zhenghong Yuan; Rong Zhang; Qiang Ding
• Keywords: Angiotensin-converting enzyme 2; Coronavirus; Tissue tropism; Pandemic

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, host range SARS-CoV-2 and intermediate hosts facilitate its transmission to humans remain unknown. interaction coronavirus with receptor key genetic determinant cross-species transmission. uses angiotensin-converting enzyme 2 (ACE2) as enter cells in species-dependent manner. In this study, we characterized ability ACE2 from diverse species support viral entry. By analyzing conservation five residues two virus-binding hotspots (hotspot 31Lys hotspot 353Lys), predicted 80 proteins mammals could potentially mediate We chose 48 orthologs among them functional analysis, showed 44 these orthologs-including domestic animals, pets, livestock, animals commonly found zoos aquaria-could bind spike protein contrast, New World monkey not further identified restricts entry using analyses. These findings highlight broad tropism might be distributed much more widely than previously recognized, underscoring necessity monitor susceptible prevent future outbreaks.