Receptor utilization of angiotensin-converting enzyme 2 (ACE2) indicates a narrower host range of SARS-CoV-2 than that of SARS-CoV
Receptor utilization of angiotensin-converting enzyme 2 (ACE2) indicates a narrower host range of SARS-CoV-2 than that of SARS-CoV
复制标题
血管紧张素转换酶 2 (ACE2) 的受体利用表明 SARS-CoV-2 的宿主范围比 SARS-CoV 更窄
DOI：
10.1111/tbed.13792
复制
发表时间：
2020
影响因子：
4.3
通讯作者：
Ge Xing-Yi
中科院分区：
文献类型：
--
作者：
Wang Qiong;Qiu Ye;Li Jin-Yan;Liao Ce-Heng;Zhou Zhi-Jian;Ge Xing-Yi
近几十年来，冠状病毒（CoV）大流行已成为全球公共卫生的巨大威胁。典型地，严重急性呼吸综合征冠状病毒（SARS-CoV）在2003年引起SARS大流行，而SARS-CoV-2引起持续的COVID-19大流行。这两种病毒都很可能起源于蝙蝠。因此，从蝙蝠到人类的直接或间接种间传播是病毒引起大流行所必需的。受体利用是决定病毒宿主范围的关键因素，对种间传播至关重要。血管紧张素转换酶2（ACE 2）是SARS冠状病毒和SARS冠状病毒2的受体，但只有某些动物的ACE 2可以被病毒利用。在这里，我们采用假病毒细胞进入试验来评估两种病毒对20只动物的ACE 2受体利用能力，发现SARS-CoV-2比SARS-CoV利用更少的ACE 2，表明SARS-CoV-2的宿主范围更窄。特别是，SARS-CoV-2倾向于不使用鼠或非哺乳动物ACE 2。与此同时，另一种SARS相关冠状病毒穿山甲-CoV在其基因组中与SARS-CoV-2高度同源，但与SARS-CoV而不是SARS-CoV-2显示出相似的ACE 2利用谱。然而，这些动物对冠状病毒的实际易感性应通过体内研究进一步验证。为了阐明受体利用的机制，我们比较了20种ACE 2的氨基酸序列，发现了5个可能对ACE 2利用至关重要的氨基酸残基，包括N末端第20和42位氨基酸残基，这些氨基酸残基可能决定SARS-CoV、SARS-CoV-2和穿山甲-CoV的不同受体利用。我们的研究加深了对大流行性冠状病毒受体利用的理解，可能有助于病原性冠状病毒的病毒追踪、中间宿主筛选和流行病预防。
Coronavirus (CoV) pandemics have become a huge threat to the public health worldwide in the recent decades. Typically, severe acute respiratory syndrome CoV (SARS‐CoV) caused SARS pandemic in 2003 and SARS‐CoV‐2 caused the ongoing COVID‐19 pandemic. Both viruses are most likely originated from bats. Thus, direct or indirect inter‐species transmission from bats to humans is required for the viruses to cause pandemics. Receptor utilization is a key factor determining the host range of viruses which is critical to the inter‐species transmission. Angiotensin‐converting enzyme 2 (ACE2) is the receptor of both SARS‐CoV and SARS‐CoV‐2, but only ACE2s of certain animals can be utilized by the viruses. Here, we employed pseudovirus cell‐entry assay to evaluate the receptor‐utilizing capability of ACE2s of 20 animals by the two viruses and found that SARS‐CoV‐2 utilized less ACE2s than SARS‐CoV, indicating a narrower host range of SARS‐CoV‐2. Especially, SARS‐CoV‐2 tended not to use murine or non‐mammal ACE2s. Meanwhile, pangolin‐CoV, another SARS‐related coronavirus highly homologous to SARS‐CoV‐2 in its genome, yet showed similar ACE2 utilization profile with SARS‐CoV rather than SARS‐CoV‐2. Nevertheless, the actual susceptibility of these animals to the coronaviruses should be further verified by in vivo studies. To clarify the mechanism underlying the receptor utilization, we compared the amino acid sequences of the 20 ACE2s and found 5 amino acid residues potentially critical for ACE2 utilization, including the N‐terminal 20th and 42nd amino acid residues that might determine the different receptor utilization of SARS‐CoV, SARS‐CoV‐2 and pangolin‐CoV. Our studies enhance the understanding of receptor utilization of pandemic coronaviruses, potentially contributing to the virus tracing, intermediate host screening and epidemic prevention for pathogenic coronaviruses.