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《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.

  • 原文来源：https://science.sciencemag.org/content/early/2020/11/04/science.abe3255
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