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Volume 38 Issue 3
June 2023

    . doi: 10.1016/j.virs.2023.04.009
    Citation: Wentao Zhu, Yuyuan Huang, Jian Gong, Lingzhi Dong, Xiaojie Yu, Haiyun Chen, Dandan Li, Libo Zhou, Jing Yang, Shan Lu. A novel bat coronavirus with a polybasic furin-like cleavage site .VIROLOGICA SINICA, 2023, 38(3) : 344-350.  http://dx.doi.org/10.1016/j.virs.2023.04.009
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    一种具有多弗林蛋白酶切割位点的新型蝙蝠冠状病毒

    • a. 首都医科大学附属北京朝阳医院;

    • b. 中国疾控中心传染病预防控制所;

    • c. 海南省疾控中心;

    • d. 中国医科科学院

    • 由SARS-CoV-2引起的新冠疫情仍在全球范围大流行，对全世界人类的健康造成了严重影响。值得关注的是，蝙蝠被认为是SARS-CoV-2最有可能的自然宿主之一。然而，目前对蝙蝠中的冠状病毒生态学认识还不是很全面。本研究中，我们运用简并引物和高通量测序技术，对海南省的112只蝙蝠携带的冠状病毒进行了筛选。结果获得了2株β冠状病毒（蝙蝠冠状病毒CD35和CD36）和1株α冠状病毒（蝙蝠冠状病毒CD30）的全长基因组。CD35与CD36的基因组相似性为99.5%，均与Bat Hp-betacoronavirus Zhejiang2013具有着最高的核苷酸同源性相似性（71.4%），其次与SARS-CoV-2最相近（54.0%）。系统进化分析显示CD35形成了一个独立的分支，并与Bat Hp-betacoronavirus Zhejiang2013聚类在一起；他们形成的大分支同时与SARS-CoV-1和SARS-CoV-2所在的分支相邻。很有意思地是，CD35和CD36拥有相同的弗林酶样的S1/S2切割位点，该位点与SARS-CoV-2的相应位点高度相似。另外，CD35受体结合域的结构与SARS-CoV-1和SARS-CoV-2的相应结构也高度相似，特别是在Loop A位置。总之，该研究丰富了我们对冠状病毒多样性的认识，同时也为SARS-CoV-2中的弗林酶切位点的自然起源提供了线索。

    A novel bat coronavirus with a polybasic furin-like cleavage site

    • a. Department of Infectious Diseases and Clinical Microbiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China;

    • b. State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China;

    • c. Hainan Provincial Center for Disease Control and Prevention, Haikou, 570203, China;

    • d. Research Units of Discovery of Unknown Bacteria and Function, Chinese Academy of Medical Sciences, Beijing, 100730, China

    • The current pandemic of COVID-19 caused by a novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), threatens human health around the world. Of particular concern is that bats are recognized as one of the most potential natural hosts of SARS-CoV-2; however, coronavirus ecology in bats is still nascent. Here, we performed a degenerate primer screening and next-generation sequencing analysis of 112 bats, collected from Hainan Province, China. Three coronaviruses, namely bat betacoronavirus (Bat CoV) CD35, Bat CoV CD36 and bat alphacoronavirus CD30 were identified. Bat CoV CD35 genome had 99.5% identity with Bat CoV CD36, both sharing the highest nucleotide identity with Bat Hp-betacoronavirus Zhejiang2013 (71.4%), followed by SARS-CoV-2 (54.0%). Phylogenetic analysis indicated that Bat CoV CD35 formed a distinct clade, and together with Bat Hp-betacoronavirus Zhejiang2013, was basal to the lineage of SARS-CoV-1 and SARS-CoV-2. Notably, Bat CoV CD35 harbored a canonical furin-like S1/S2 cleavage site that resembles the corresponding sites of SARS-CoV-2. The furin cleavage sites between CD35 and CD36 are identical. In addition, the receptor-binding domain of Bat CoV CD35 showed a highly similar structure to that of SARS-CoV-1 and SARS-CoV-2, especially in one binding loop. In conclusion, this study deepens our understanding of the diversity of coronaviruses and provides clues about the natural origin of the furin cleavage site of SARS-CoV-2.
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      A novel bat coronavirus with a polybasic furin-like cleavage site

        Corresponding author: Jing Yang, yangjing@icdc.cn
        Corresponding author: Shan Lu, lushan@icdc.cn
      • a. Department of Infectious Diseases and Clinical Microbiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China;
      • b. State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China;
      • c. Hainan Provincial Center for Disease Control and Prevention, Haikou, 570203, China;
      • d. Research Units of Discovery of Unknown Bacteria and Function, Chinese Academy of Medical Sciences, Beijing, 100730, China
      • Received Date: 07 January 2023
      • Accepted Date: 24 April 2023

      Abstract: The current pandemic of COVID-19 caused by a novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), threatens human health around the world. Of particular concern is that bats are recognized as one of the most potential natural hosts of SARS-CoV-2; however, coronavirus ecology in bats is still nascent. Here, we performed a degenerate primer screening and next-generation sequencing analysis of 112 bats, collected from Hainan Province, China. Three coronaviruses, namely bat betacoronavirus (Bat CoV) CD35, Bat CoV CD36 and bat alphacoronavirus CD30 were identified. Bat CoV CD35 genome had 99.5% identity with Bat CoV CD36, both sharing the highest nucleotide identity with Bat Hp-betacoronavirus Zhejiang2013 (71.4%), followed by SARS-CoV-2 (54.0%). Phylogenetic analysis indicated that Bat CoV CD35 formed a distinct clade, and together with Bat Hp-betacoronavirus Zhejiang2013, was basal to the lineage of SARS-CoV-1 and SARS-CoV-2. Notably, Bat CoV CD35 harbored a canonical furin-like S1/S2 cleavage site that resembles the corresponding sites of SARS-CoV-2. The furin cleavage sites between CD35 and CD36 are identical. In addition, the receptor-binding domain of Bat CoV CD35 showed a highly similar structure to that of SARS-CoV-1 and SARS-CoV-2, especially in one binding loop. In conclusion, this study deepens our understanding of the diversity of coronaviruses and provides clues about the natural origin of the furin cleavage site of SARS-CoV-2.

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