登录
 机构网站
  1. 首页
  2. 情报产品
  3. 快讯详情

《bioRxiv，6月2日，An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction》

  • 来源专题：COVID-19科研动态监测
  • 编译者： xuwenwhlib
  • 发布时间：2020-06-03

  • An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction
    View ORCID ProfileLeo Hanke, Maria Laura Perez Vidakovics, Daniel Sheward, Hrishikesh Das, Tim Schulte, Ainhoa Moliner Morro, Martin Corcoran, Adnane Achour,  View ORCID ProfileGunilla Karlsson Hedestam,  View ORCID ProfileB. Martin Hällberg, Ben Murrell,  View ORCID ProfileGerald M McInerney
    doi: https://doi.org/10.1101/2020.06.02.130161

    Abstract
    We report the isolation and characterization of an alpaca-derived, single domain antibody fragment (nanobody) that specifically targets the receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein (spike) and potently neutralizes the virus. A cryo-electron microscopy structure of the bound complex at 2.9 Å resolution reveals that the nanobody (Ty1) binds to an epitope on the RBD accessible in both the "up" and "down" conformations and that Ty1 sterically hinders RBD-ACE2 binding. Mechanistic characterization confirms that Ty1 directly interferes with host cell receptor binding. This 12.8 kDa nanobody binds the SARS-CoV-2 spike with high specificity and affinity, and can be produced in high quantities recombinantly thereby offering potential as a potent and widely accessible SARS-CoV-2 antiviral agent.

  • 原文来源：https://www.biorxiv.org/content/10.1101/2020.06.02.130161v1
134浏览量
原文链接
相关报告

  • 《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.
    138浏览量
    原文链接

  • 《bioRxiv，6月10日，Potent synthetic nanobodies against SARS-CoV-2 and molecular basis for neutralization》
    • 来源专题：COVID-19科研动态监测
    • 编译者：xuwenwhlib
    • 发布时间：2020-06-11
    • Potent synthetic nanobodies against SARS-CoV-2 and molecular basis for neutralization View ORCID ProfileDianfan Li, View ORCID ProfileTingting Li, View ORCID ProfileHongmin Cai, View ORCID ProfileHebang Yao, View ORCID ProfileBingjie Zhou, Yapei Zhao, View ORCID ProfileWenming Qin, View ORCID ProfileCedric A.J. Hutter, Yanling Lai, Juan Bao, Jiaming Lan, Gary Wong, View ORCID ProfileMarkus Seeger, View ORCID ProfileDimitri Lavillette doi: https://doi.org/10.1101/2020.06.09.143438 Abstract SARS-CoV-2, the Covid-19 causative virus, adheres to human cells through binding of its envelope Spike protein to the receptor ACE2. The Spike receptor-binding domain (S-RBD) mediates this key event and thus is a primary target for therapeutic neutralizing antibodies to mask the ACE2-interacting interface. Here, we generated 99 synthetic nanobodies (sybodies) using ribosome and phage display. The best sybody MR3 binds the RBD with KD of 1.0 nM and neutralizes SARS-CoV-2 pseudovirus with IC50 of 0.40 μg/mL. Crystal structures of two sybody-RBD complexes reveal a common neutralizing mechanism through which the RBD-ACE2 interaction is competitively inhibited by sybodies. The structures allowed the rational design of a mutant with higher affinity and improved neutralization efficiency by ≈24-folds, lowering the IC50 from 12.32 to 0.50 μg/mL. Further, the structures explain the selectivity of sybodies between SARS-CoV strains. Our work presents an alternative approach to generate neutralizers against newly emerged viruses.
    105浏览量
    原文链接