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Reply to Hayashi and Konishi: Noneffect of SARS-CoV-2 spike glycoprotein Y217N mutation on affinity between virus and ACE2

  • Yan-Dong Tang
    Correspondence
    For correspondence: Yan-Dong Tang
    Affiliations
    State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin, China
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Open AccessPublished:May 31, 2021DOI:https://doi.org/10.1016/j.jbc.2021.100706
      We thank Hayashi and Konishi for their comments and interest in our article (
      • Zhang H.L.
      • Li Y.M.
      • Sun J.
      • Zhang Y.Y.
      • Wang T.Y.
      • Sun M.X.
      • Wang M.H.
      • Yang Y.L.
      • Hu X.L.
      • Tang Y.D.
      • Zhao J.
      • Cai X.
      Evaluating angiotensin-converting enzyme 2-mediated SARS-CoV-2 entry across species.
      ). We agree that by structural modeling analysis, angiotensin-converting enzyme 2 (ACE2 [Y217N]) mutant shows no changes in binding with receptor-binding domain (RBD) when compared with WT ACE2, which is depicted in Figure 4 in our article. We think the lower binding affinity of human ACE2 N217 with RBD was due to the following reasons. First, cell surface abundance of ACE2 Y217N was less compared with WT ACE2 (Fig. 5 in our article). Second, although cell surface abundance of ACE2 Y217N decreased, there were more than 20% of cells with ACE2 positive. Nevertheless, when quantified by Western blot, RBD binding was extremely low (Fig. 3 in our article). Therefore, we think human ACE2 N217 lost the binding ability to RBD and speculated that introducing Y217N mutation may alter the folding and conformational structure of ACE2. However, this needs to be investigated further.

      Conflict of interest

      The author declares no conflicts of interests with the contents of this article.

      Reference

        • Zhang H.L.
        • Li Y.M.
        • Sun J.
        • Zhang Y.Y.
        • Wang T.Y.
        • Sun M.X.
        • Wang M.H.
        • Yang Y.L.
        • Hu X.L.
        • Tang Y.D.
        • Zhao J.
        • Cai X.
        Evaluating angiotensin-converting enzyme 2-mediated SARS-CoV-2 entry across species.
        J. Biol. Chem. 2021; 296: 100435

      Linked Article

      • Evaluating angiotensin-converting enzyme 2-mediated SARS-CoV-2 entry across species
        Journal of Biological ChemistryVol. 296
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          The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic represents a global threat, and the interaction between the virus and angiotensin-converting enzyme 2 (ACE2), the primary entry receptor for SARS-CoV-2, is a key determinant of the range of hosts that can be infected by the virus. However, the mechanisms underpinning ACE2-mediated viral entry across species remains unclear. Using infection assay, we evaluated SARS-CoV-2 entry mediated by ACE2 of 11 different animal species.
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      • Noneffect of SARS-CoV-2 spike glycoprotein Y217N mutation on affinity between the virus and ACE2
        Journal of Biological ChemistryVol. 296
        • Preview
          The interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and angiotensin-converting enzyme 2 (ACE2), the primary entry receptor for SARS-CoV-2, is a key determinant of the range of hosts that can be infected by the virus. Zhang et al. (1) reportedly constructed human ACE2 (hACE2) with the Y217N mutation and found that this mutation completely blocked SARS-CoV-2 entry. Zhang et al. (1) performed an receptor binding domain (RBD) binding assay and found that WT hACE2 potently bound the RBD; however, hACE2 Y217N almost lost the ability to bind the RBD.
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        Open Access