登录
 机构网站
  1. 首页
  2. 情报产品
  3. 快讯详情

《Nature，9月11日，Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor》

  • 来源专题：COVID-19科研动态监测
  • 编译者： zhangmin
  • 发布时间：2020-09-16

  • Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor

    Jinsung Yang, Simon J. L. Petitjean, Melanie Koehler, Qingrong Zhang, Andra C. Dumitru, Wenzhang Chen, Sylvie Derclaye, Stéphane P. Vincent, Patrice Soumillion & David Alsteens

    Nature Communications volume 11, Article number: 4541 (2020)

    Abstract

    Study of the interactions established between the viral glycoproteins and their host receptors is of critical importance for a better understanding of virus entry into cells. The novel coronavirus SARS-CoV-2 entry into host cells is mediated by its spike glycoprotein (S-glycoprotein), and the angiotensin-converting enzyme 2 (ACE2) has been identified as a cellular receptor. Here, we use atomic force microscopy to investigate the mechanisms by which the S-glycoprotein binds to the ACE2 receptor. We demonstrate, both on model surfaces and on living cells, that the receptor binding domain (RBD) serves as the binding interface within the S-glycoprotein with the ACE2 receptor and extract the kinetic and thermodynamic properties of this binding pocket. Altogether, these results provide a picture of the established interaction on living cells. Finally, we test several binding inhibitor peptides targeting the virus early attachment stages, offering new perspectives in the treatment of the SARS-CoV-2 infection.

  • 原文来源：https://www.nature.com/articles/s41467-020-18319-6
48浏览量
原文链接
相关报告

  • 《Nature，3月30日，Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2020-03-31
    • Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor Jun Lan, Jiwan Ge, Jinfang Yu, Sisi Shan, Huan Zhou, Shilong Fan, Qi Zhang, Xuanling Shi, Qisheng Wang, Linqi Zhang & Xinquan Wang Nature (2020) Abstract A novel and highly pathogenic coronavirus (SARS-CoV-2) has caused an outbreak in Wuhan city, Hubei province of China since December 2019, and soon spread nationwide and spilled over to other countries around the world1–3. To better understand the initial step of infection at an atomic level, we determined the crystal structure of the SARS-CoV-2 spike receptor-binding domain (RBD) bound to the cell receptor ACE2 at 2.45 Å resolution. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also utilizes ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are critical for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD.
    200浏览量
    原文链接

  • 《Nature，9月17日，Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2020-10-13
    • Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion Donald J. Benton, Antoni G. Wrobel, Pengqi Xu, Chloë Roustan, Stephen R. Martin, Peter B. Rosenthal, John J. Skehel & Steven J. Gamblin Nature (2020) Abstract SARS-CoV-2 infection is initiated by virus binding to ACE2 cell surface receptors1–4, followed by fusion of virus and cell membranes to release the virus genome into the cell. Both receptor binding and membrane fusion activities are mediated by the virus Spike glycoprotein, S5–7. As with other class I membrane fusion proteins, S is post-translationally cleaved, in this case by furin, into S1 and S2 components that remain associated following cleavage8–10. Fusion activation following receptor binding is proposed to involve the exposure of a second proteolytic site (S2’), cleavage of which is required for the fusion peptide release11,12. We have investigated the binding of ACE2 to the furin-cleaved form of SARS-CoV-2 S by cryoEM. We classify ten different molecular species including the unbound, closed spike trimer, the fully open ACE2-bound trimer, and dissociated monomeric S1 bound to ACE2. The ten structures describe ACE2 binding events which destabilise the spike trimer, progressively opening up, and out, the individual S1 components. The opening process reduces S1 contacts and un-shields the trimeric S2 core, priming fusion activation and dissociation of ACE2-bound S1 monomers. The structures also reveal refolding of an S1 subdomain following ACE2 binding, that disrupts interactions with S2, notably involving Asp61413–15, leading to destabilisation of the structure of S2 proximal to the secondary (S2’) cleavage site.
    171浏览量
    原文链接