《Cell,3月16日,N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2》

  • 来源专题:COVID-19科研动态监测
  • 编译者: zhangmin
  • 发布时间:2021-03-23
  • N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2
    Matthew McCallum #
    Anna De Marco #
    Florian A. Lempp
    Davide Corti
    Matteo Samuele Pizzuto
    David Veesler %
    Show all authors
    Show footnotes
    Published:March 16, 2021DOI:https://doi.org/10.1016/j.cell.2021.03.028

    Summary
    The SARS-CoV-2 spike (S) glycoprotein contains an immunodominant receptor-binding domain (RBD) targeted by most neutralizing antibodies (Abs) in COVID-19 patient plasma. Little is known about neutralizing Abs binding to epitopes outside the RBD and their contribution to protection. Here, we describe 41 human monoclonal Abs (mAbs) derived from memory B cells, which recognize the SARS-CoV-2 S N-terminal domain (NTD) and show that a subset of them neutralize SARS-CoV-2 ultrapotently. We define an antigenic map of the SARS-CoV-2 NTD and identify a supersite (designated site i) recognized by all known NTD-specific neutralizing mAbs. These mAbs inhibit cell-to-cell fusion, activate effector functions, and protect Syrian hamsters from SARS-CoV-2 challenge, albeit selecting escape mutants in some animals. Indeed, several SARS-CoV-2 variants, including the B.1.1.7, B.1.351 and P1 lineages, harbor frequent mutations within the NTD supersite suggesting ongoing selective pressure and the importance of NTD-specific neutralizing mAbs for protective immunity and vaccine design.

  • 原文来源:https://www.cell.com/cell/fulltext/S0092-8674(21)00356-1
相关报告
  • 《Cell,3月16日,Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein》

    • 来源专题:COVID-19科研动态监测
    • 编译者:zhangmin
    • 发布时间:2021-03-23
    • Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein Naveenchandra Suryadevara # Swathi Shrihari # Pavlo Gilchuk Larissa B. Thackray Michael S. Diamond James E. Crowe Jr. Show all authors Show footnotes Published:March 16, 2021DOI:https://doi.org/10.1016/j.cell.2021.03.029 Summary Most human monoclonal antibodies (mAbs) neutralizing SARS-CoV-2 recognize the spike (S) protein receptor-binding domain and block virus interactions with the cellular receptor angiotensin-converting enzyme 2. We describe a panel of human mAbs binding to diverse epitopes on the N-terminal domain (NTD) of S protein from SARS-CoV-2 convalescent donors and found a minority of these possessed neutralizing activity. Two mAbs (COV2-2676 and COV2-2489) inhibited infection of authentic SARS-CoV-2 and recombinant VSV/SARS-CoV-2 viruses. We mapped their binding epitopes by alanine-scanning mutagenesis and selection of functional SARS-CoV-2 S neutralization escape variants. Mechanistic studies showed that these antibodies neutralize in part by inhibiting a post-attachment step in the infection cycle. COV2-2676 and COV2-2489 offered protection either as prophylaxis or therapy, and Fc effector functions were required for optimal protection. Thus, natural infection induces a subset of potent NTD-specific mAbs that leverage neutralizing and Fc-mediated activities to protect against SARS-CoV-2 infection using multiple functional attributes.
  • 《BioRxiv,3月17日,A Cryptic Site of Vulnerability on the Receptor Binding Domain of the SARS-CoV-2 Spike Glycoprotein》

    • 来源专题:COVID-19科研动态监测
    • 编译者:zhangmin
    • 发布时间:2020-03-18
    • A Cryptic Site of Vulnerability on the Receptor Binding Domain of the SARS-CoV-2 Spike Glycoprotein M. Gordon Joyce, Rajeshwer S Sankhala, Wei-Hung Chen, Misook Choe, Hongjun Bai, Agnes Hajduczki, Lianying Yan, Spencer L Sterling, Caroline Peterson, Ethan C Green, Clayton Smith, Natalia de Val, Mihret Amare, Paul Scott, Eric D Laing, Christopher C Broder, Morgane Rolland, Nelson L Michael, Kayvon Modjarrad doi: https://doi.org/10.1101/2020.03.15.992883 Abstract SARS-CoV-2 is a zoonotic virus that has caused a pandemic of severe respiratory disease—COVID-19—within several months of its initial identification. Comparable to the first SARS-CoV, this coronaviruses surface Spike (S) glycoprotein mediates cell entry via the human ACE-2 receptor, and, thus, is the principal target for the development of vaccines and immunotherapeutics. Molecular information on the SARS-CoV-2 S glycoprotein remains limited. Here we report the crystal structure of the SARS-CoV-2 S receptor-binding-domain (RBD) at a the highest resolution to date, of 1.95 Å. We identified a set of SARS-reactive monoclonal antibodies with cross-reactivity to SARS-CoV-2 RBD and other betacoronavirus S glycoproteins. *注,本文为预印本论文手稿,是未经同行评审的初步报告,其观点仅供科研同行交流,并不是结论性内容,请使用者谨慎使用.