2. Academic Validation
  3. Identification of Human Single-Domain Antibodies against SARS-CoV-2

Identification of Human Single-Domain Antibodies against SARS-CoV-2

  • Cell Host Microbe. 2020 Jun 10;27(6):891-898.e5. doi: 10.1016/j.chom.2020.04.023.
Yanling Wu 1,  Cheng Li 2,  Shuai Xia 2,  Xiaolong Tian 2,  Yu Kong 2,  Zhi Wang 2,  Chenjian Gu 2,  Rong Zhang 2,  Chao Tu 3,  Youhua Xie 2,  Zhenlin Yang 4,  Lu Lu 2,  Shibo Jiang 2,  Tianlei Ying 5
Affiliations

Affiliations

  • 1 MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: [email protected].
  • 2 MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
  • 3 Biomissile Corporation, Shanghai 201203, China.
  • 4 Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
  • 5 MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: [email protected].
PMID: 32413276 DOI: 10.1016/j.chom.2020.04.023
Abstract

The worldwide spread of COVID-19 highlights the need for an efficient approach to rapidly develop therapeutics and prophylactics against SARS-CoV-2. The SARS-CoV-2 spike protein, containing the receptor-binding domain (RBD) and S1 subunit involved in receptor engagement, is a potential therapeutic target. We describe the development of a phage-displayed single-domain antibody library by grafting naive complementarity-determining regions (CDRs) into framework regions of a human germline immunoglobulin heavy chain variable region (IGHV) allele. Panning this library against SARS-CoV-2 RBD and S1 subunit identified fully human single-domain Antibodies targeting five distinct epitopes on SARS-CoV-2 RBD with subnanomolar to low nanomolar affinities. Some of these Antibodies neutralize SARS-CoV-2 by targeting a cryptic epitope located in the spike trimeric interface. Collectively, this work presents a versatile platform for rapid antibody isolation and identifies promising therapeutic anti-SARS-CoV-2 Antibodies as well as the diverse immogneic profile of the spike protein.

Keywords

CR3022; RBD; SARS-CoV-2; nanobody; single-domain antibody; trimeric interface.

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