Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptor.

Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptor.
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鉴定使用BAT ACE2受体的新型谱系蝙蝠SARS相关的冠状病毒。

DOI:
10.1080/22221751.2021.1956373
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发表时间:
2021-12
影响因子:
13.2
通讯作者:
Shi ZL
Shi ZL
中科院分区:
医学2区
文献类型:
--
作者:
Guo H;Hu B;Si HR;Zhu Y;Zhang W;Li B;Li A;Geng R;Lin HF;Yang XL;Zhou P;Shi ZL

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严重呼吸道疾病冠状病毒2(SARS-CoV-2)已成为本世纪最具破坏性的新冠肺炎疾病。SARS-CoV-2尚未解决的科学问题之一是这种病毒的动物来源。蝙蝠和穿山甲被认为是最有可能携带高度相似的SARS-CoV-2相关病毒(SARSR-CoV-2)的宿主。这项研究从2015年我们发现RaTG13的同一地点的蝙蝠身上发现了一种新的SARSR-CoV谱系,包括RaTG15和其他七种病毒。虽然RaTG15及相关病毒与SARS-CoV-2在保守的ORF1b区有97.2%的氨基酸序列同源性,但在基因组水平上与所有已知的SARSR-CoV的核苷酸同源性不到77.6%,从而形成了一个独特的系统发育树。我们发现RaTG15受体结合域(RBD)可以与马来亚穿山甲的ACE2结合,并将其用作进入受体,但人类的ACE2除外。然而,它包含一个短的缺失,并具有不同的负责ACE2结合的关键残基。此外,我们还发现,在已发现的蝙蝠SARSR-CoV-2谱系中,没有一种病毒像穿山甲衍生的SARSR-CoV-2或SARSR-CoV-1谱系中的某些病毒那样有效地利用人类ACE2。因此,需要对蝙蝠进行进一步的系统和纵向研究,以防止未来由SARSR-CoV引起的溢出事件或更好地了解SARS-CoV-2的起源。
Severe respiratory disease coronavirus-2 (SARS-CoV-2) has been the most devastating disease COVID-19 in the century. One of the unsolved scientific questions of SARS-CoV-2 is the animal origin of this virus. Bats and pangolins are recognized as the most probable reservoir hosts that harbour highly similar SARS-CoV-2 related viruses (SARSr-CoV-2). This study identified a novel lineage of SARSr-CoVs, including RaTG15 and seven other viruses, from bats at the same location where we found RaTG13 in 2015. Although RaTG15 and the related viruses share 97.2% amino acid sequence identities with SARS-CoV-2 in the conserved ORF1b region, it only shows less than 77.6% nucleotide identity to all known SARSr-CoVs at the genome level, thus forming a distinct lineage in the Sarbecovirus phylogenetic tree. We found that the RaTG15 receptor-binding domain (RBD) can bind to ACE2 from Rhinolophus affinis, Malayan pangolin, and use it as an entry receptor, except for ACE2 from humans. However, it contains a short deletion and has different key residues responsible for ACE2 binding. In addition, we showed that none of the known viruses in bat SARSr-CoV-2 lineage discovered uses human ACE2 as efficiently as the pangolin-derived SARSr-CoV-2 or some viruses in the SARSr-CoV-1 lineage. Therefore, further systematic and longitudinal studies in bats are needed to prevent future spillover events caused by SARSr-CoVs or to understand the origin of SARS-CoV-2 better.
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