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《CELL，5月5日，Identification of human single-domain antibodies against SARS-CoV-2》

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

  • Identification of human single-domain antibodies againstSARS-CoV-2

    Yanling Wu,Cheng Li,Shuai Xia,Xiaolong Tian,Yu Kong,Zhi Wang,Chenjian Gu,Rong Zhang,Chao Tu,2 Youhua Xie,1 Zhenlin Yang,3 Lu Lu,1Shibo

    Jiang,Tianlei Ying1,4 5 *

    SUMMARY

    The worldwide spread of COVID-19 highlights the need for an efficient approach torapidly develop therapeutics and prophylactics against SARS-CoV-2. TheSARS-CoV-2 spike protein, containing the receptor-binding domain (RBD) and S1subunit involved in receptor engagement, is a potential therapeutic target. We describethe development of a phage-displayed single-domain antibody library by graftingnaïve complementarity-determining regions (CDRs) into framework regions of ahuman germline immunoglobulin heavy chain variable region (IGHV) allele. Panningthis library against SARS-CoV-2 RBD and S1 subunit identified fully humansingle-domain antibodies targeting five distinct epitopes on SARS-CoV-2 RBD withsubnanomolar to low nanomolar affinities. Some of these antibodies neutralizeSARS-CoV-2 by targeting a cryptic epitope located in the spike trimeric interfaCollectively, this work presents a versatile platform for rapid antibody isolation andidentifies promising therapeutic anti-SARS-CoV-2 antibodies as well as the diverseimmogneic profile of the spike protein

  • 原文来源：https://marlin-prod.literatumonline.com/pb-assets/products/coronavirus/chom2310_s50.pdf
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  • 《BioRxiv，3月31日，Fully human single-domain antibodies against SARS-CoV-2》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2020-04-01
    • Fully human single-domain antibodies against SARS-CoV-2 Yanling Wu, Cheng Li, Shuai Xia, Xiaolong Tian, Zhi Wang, Yu Kong, Chenjian Gu, Rong Zhang, Chao Tu, Youhua Xie, Lu Lu, Shibo Jiang, Tianlei Ying doi: https://doi.org/10.1101/2020.03.30.015990 Abstract The COVID-19 pandemic is spreading rapidly, highlighting the urgent need for an efficient approach to rapidly develop therapeutics and prophylactics against SARS-CoV-2. We describe here the development of a phage-displayed single-domain antibody library by grafting naive CDRs into framework regions of an identified human germline IGHV allele. This enabled the isolation of high-affinity single-domain antibodies of fully human origin. The panning using SARS-CoV-2 RBD and S1 as antigens resulted in the identification of antibodies targeting five types of neutralizing or non-neutralizing epitopes on SARS-CoV-2 RBD. These fully human single-domain antibodies bound specifically to SARS-CoV-2 RBD with subnanomolar to low nanomolar affinities. *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.
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  • 《CELL，4月21日， Structural Basis for Potent Neutralization of Betacoronaviruses by Single-domain Camelid Antibodies》
    • 来源专题：COVID-19科研动态监测
    • 编译者：xuwenwhlib
    • 发布时间：2020-04-21
    • Structural Basis for Potent Neutralization of Betacoronaviruses by Single-domain Camelid Antibodies Authors: Daniel Wrapp1#, Dorien De Vlieger2,3,4# , Kizzmekia S. Corbett5 Gretel M. Torres6 Nianshuang Wang1 , Wander Van Breedam2,3, Kenny Roose2,3, Loes van Schie2,3, VIB-CMB COVID-19 Response Team, Markus Hoffmann Stefan PöhlmannBarney S. Graham5 Nico Callewaert2,3 Ber Schepens2,3,4*, Xavier Saelens2,3,4* and Jason S. McLellan SUMMARY Coronaviruses make use of a large envelope protein called spike (S) to engage host cell receptors and catalyze membrane fusion. Because of the vital role that these S proteins play, they represent a vulnerable target for the development of therapeutics. Here, we describe the isolation of singledomain antibodies (VHHs) from a llama immunized with prefusion-stabilized coronavirus spikes. These VHHs neutralize MERS-CoV or SARS-CoV-1 S pseudotyped viruses,respectively. Crystal structures of these VHHs bound to their respective viral targets reveal two distinct epitopes, but both VHHs interfere with receptor binding. We also show cross-reactivity between the SARS-CoV-1 S-directed VHH and SARS-CoV-2 S, and demonstrate that this crossreactive VHH neutralizes SARS-CoV-2 S pseudotyped viruses as a bivalent human IgG Fcfusion. These data provide a molecular basis for the neutralization of pathogenic betacoronaviruses by VHHs and suggest that these molecules may serve as useful therapeutics during coronavirus outbreaks.
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