登录
 机构网站
  1. 首页
  2. 情报产品
  3. 快讯详情

《Science，5月4日，Site-specific glycan analysis of the SARS-CoV-2 spike》

  • 来源专题：COVID-19科研动态监测
  • 编译者： xuwenwhlib
  • 发布时间：2020-05-06

  • Site-specific glycan analysis of the SARS-CoV-2 spike

    Yasunori Watanabe1,2,3,*, Joel D. Allen1,*, Daniel Wrapp4, Jason S. McLellan4, Max Crispin1,†

    See all authors and affiliations

    Science 04 May 2020:

    eabb9983

    DOI: 10.1126/science.abb9983

    Abstract

    The emergence of the betacoronavirus, SARS-CoV-2, the causative agent of COVID-19, represents a significant threat to global human health. Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion. SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion. Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen. This analysis enables mapping of the glycan-processing states across the trimeric viral spike. We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.

  • 原文来源：https://science.sciencemag.org/content/early/2020/05/01/science.abb9983
115浏览量
原文链接
相关报告

  • 《Science Advances，10月20日，Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2020-11-16
    • Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate View ORCID ProfileSandhya Bangaru1, View ORCID ProfileGabriel Ozorowski1, Hannah L. Turner1, View ORCID ProfileAleksandar Antanasijevic1, View ORCID ProfileDeli Huang2, View ORCID ProfileXiaoning... Science 20 Oct 2020: eabe1502 DOI: 10.1126/science.abe1502 Abstract Vaccine efforts against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the current COVID-19 pandemic are focused on SARS-CoV-2 spike glycoprotein, the primary target for neutralizing antibodies. We performed cryo-EM and site-specific glycan analysis of one of the leading subunit vaccine candidates from Novavax based on a full-length spike protein formulated in polysorbate 80 (PS 80) detergent. Our studies reveal a stable prefusion conformation of the spike immunogen with slight differences in the S1 subunit compared to published spike ectodomain structures. We also observed novel interactions between the spike trimers allowing formation of higher order spike complexes. This study confirms the structural integrity of the full-length spike protein immunogen and provides a basis for interpreting immune responses to this multivalent nanoparticle immunogen.
    132浏览量
    原文链接

  • 《Science，11月5日，An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2020-11-18
    • An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike View ORCID ProfileMichael Schoof1,2,*,†, View ORCID ProfileBryan Faust1,2,3,4,*, View ORCID ProfileReuben A. Saunders1,5,*, View ORCID ProfileSmriti Sangwan1,2,*, View ORCID ProfileVeronica Rezelj6,*,... Science 05 Nov 2020: eabe3255 DOI: 10.1126/science.abe3255 Abstract The SARS-CoV-2 virus enters host cells via an interaction between its Spike protein and the host cell receptor angiotensin converting enzyme 2 (ACE2). By screening a yeast surface-displayed library of synthetic nanobody sequences, we developed nanobodies that disrupt the interaction between Spike and ACE2. Cryogenic electron microscopy (cryo-EM) revealed that one nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains (RBDs) locked into their inaccessible down-state, incapable of binding ACE2. Affinity maturation and structure-guided design of multivalency yielded a trivalent nanobody, mNb6-tri, with femtomolar affinity for Spike and picomolar neutralization of SARS-CoV-2 infection. mNb6-tri retains function after aerosolization, lyophilization, and heat treatment, which enables aerosol-mediated delivery of this potent neutralizer directly to the airway epithelia.
    182浏览量
    原文链接