A SARS-CoV-2 neutralizing antibody discovery by single cell sequencing and molecular modeling

Zheyue Wang; Qi Tang; Bende Liu; Wenqing Zhang; Yufeng Chen; Ningfei Ji; Yan Peng; Xiaohui Yang; Daixun Cui; Weiyu Kong; Xiaojun Tang; Tingting Yang; Mingshun Zhang; Xinxia Chang; Jin Zhu; Mao Huang; Zhenqing Feng

doi:10.7555/JBR.36.20220221

Volume 37 Issue 3

May 2023

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Article Navigation > The Journal of Biomedical Research > 2023 > 37(3): 166-178

Zheyue Wang, Qi Tang, Bende Liu, Wenqing Zhang, Yufeng Chen, Ningfei Ji, Yan Peng, Xiaohui Yang, Daixun Cui, Weiyu Kong, Xiaojun Tang, Tingting Yang, Mingshun Zhang, Xinxia Chang, Jin Zhu, Mao Huang, Zhenqing Feng. A SARS-CoV-2 neutralizing antibody discovery by single cell sequencing and molecular modeling[J]. The Journal of Biomedical Research, 2023, 37(3): 166-178. doi: 10.7555/JBR.36.20220221

Citation:

Zheyue Wang, Qi Tang, Bende Liu, Wenqing Zhang, Yufeng Chen, Ningfei Ji, Yan Peng, Xiaohui Yang, Daixun Cui, Weiyu Kong, Xiaojun Tang, Tingting Yang, Mingshun Zhang, Xinxia Chang, Jin Zhu, Mao Huang, Zhenqing Feng. A SARS-CoV-2 neutralizing antibody discovery by single cell sequencing and molecular modeling[J]. The Journal of Biomedical Research, 2023, 37(3): 166-178. doi: 10.7555/JBR.36.20220221

Citation:

Zheyue Wang, Qi Tang, Bende Liu, Wenqing Zhang, Yufeng Chen, Ningfei Ji, Yan Peng, Xiaohui Yang, Daixun Cui, Weiyu Kong, Xiaojun Tang, Tingting Yang, Mingshun Zhang, Xinxia Chang, Jin Zhu, Mao Huang, Zhenqing Feng. A SARS-CoV-2 neutralizing antibody discovery by single cell sequencing and molecular modeling[J]. The Journal of Biomedical Research, 2023, 37(3): 166-178. doi: 10.7555/JBR.36.20220221

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A SARS-CoV-2 neutralizing antibody discovery by single cell sequencing and molecular modeling

doi: 10.7555/JBR.36.20220221

Zheyue Wang^{1, △},
Qi Tang^{1, △},
Bende Liu^{2, △},
Wenqing Zhang¹,
Yufeng Chen¹,
Ningfei Ji³,
Yan Peng¹,
Xiaohui Yang¹,
Daixun Cui¹,
Weiyu Kong¹,
Xiaojun Tang⁴,
Tingting Yang¹,
Mingshun Zhang¹,
Xinxia Chang¹,
Jin Zhu^{5
,
,},
Mao Huang^{3
,
,},
Zhenqing Feng^{1, 6
,
,}

1.
National Health Commission Key Laboratory of Antibody Technique, Jiangsu Province Engineering Research Center of Antibody Drug, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 211166, China
2.
Department of Cardiology, the First People's Hospital of Jiangxia District, Wuhan, Hubei 430299, China
3.
Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
4.
Department of Rheumatology and Immunology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China
5.
Huadong Medical Institute of Biotechniques, Nanjing, Jiangsu 210028, China
6.
Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China

More Information

Corresponding author: Jin Zhu, Huadong Medical Institute of Biotechniques, 293 Zhongshan Road, Nanjing, Jiangsu 210028, China. Tel: +86-25-84514223, E-mail: zhujin1968@njmu.edu.cn; Mao Huang, Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China. Tel: +86-25-83718836, E-mail: hm6114@163.com; Zhenqing Feng, National Health Commission Key Laboratory of Antibody Technique, Jiangsu Province Engineering Research Center of Antibody Drug, Department of Pathology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu 211166, China. Tel: +86-25-86869411, E-mail: fengzhenqing@njmu.edu.cn
Received: 2022-10-05
Revised: 2022-12-06
Accepted: 2022-12-09

Published: 2022-12-12

Issue Date: 2023-05-28

Abstract

Abstract

Although vaccines have been developed, mutations of SARS-CoV-2, especially the dominant B.1.617.2 (delta) and B.1.529 (omicron) strains with more than 30 mutations on their spike protein, have caused a significant decline in prophylaxis, calling for the need for drug improvement. Antibodies are drugs preferentially used in infectious diseases and are easy to get from immunized organisms. The current study combined molecular modeling and single memory B cell sequencing to assess candidate sequences before experiments, providing a strategy for the fabrication of SARS-CoV-2 neutralizing antibodies. A total of 128 sequences were obtained after sequencing 196 memory B cells, and 42 sequences were left after merging extremely similar ones and discarding incomplete ones, followed by homology modeling of the antibody variable region. Thirteen candidate sequences were expressed, of which three were tested positive for receptor binding domain recognition but only one was confirmed as having broad neutralization against several SARS-CoV-2 variants. The current study successfully obtained a SARS-CoV-2 antibody with broad neutralizing abilities and provided a strategy for antibody development in emerging infectious diseases using single memory B cell BCR sequencing and computer assistance in antibody fabrication.
- SARS-CoV-2,
- neutralizing antibody,
- single B cell BCR sequencing,
- molecular modeling

CLC number: R392, Document code: A
The authors reported no conflict of interests.
△These authors contributed equally to this work.

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References(41)

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