生物医学研究杂志(英文版)2023,Vol.37Issue(3) :166-178.

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
生物医学研究杂志(英文版)2023,Vol.37Issue(3) :166-178.

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

Zheyue Wang 1Qi Tang 1Bende Liu 2Wenqing Zhang 1Yufeng Chen 1Ningfei Ji 3Yan Peng 1Xiaohui Yang 1Daixun Cui 1Weiyu Kong 1Xiaojun Tang 4Tingting Yang 1Mingshun Zhang 1Xinxia Chang 1Jin Zhu 5Mao Huang 3Zhenqing Feng6
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作者信息

  • 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. 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;Jiangsu Key Lab of Cancer Biomarkers,Prevention and Treatment,Collaborative Innovation Center for Cancer Personalized Medicine,Nanjing Medical University,Nanjing,Jiangsu 211166,China
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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.

Key words

SARS-CoV-2/neutralizing antibody/single B cell BCR sequencing/molecular modeling

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基金项目

Jiangsu Provincial Key Research and Development Program(BE2020616)

National Key R&D Program of China(2018YFC1200603)

National Science and Technology Major Project(2019SWAQ05-5-4)

Jiangsu Key Lab of Cancer Biomarkers,Prevention and Treatment,Collaborative Innovation Center for Cancer Personalized Medicine,N()

出版年

2023
生物医学研究杂志(英文版)
南京医科大学

生物医学研究杂志(英文版)

CSCD北大核心
影响因子:0.794
ISSN:1674-8301
参考文献量41
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