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

作     者：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 

作者机构：National Health Commission Key Laboratory of Antibody TechniqueJiangsu Province Engineering Research Center of Antibody DrugDepartment of PathologyNanjing Medical UniversityNanjingJiangsu 211166China Department of Cardiologythe First People's Hospital of Jiangxia DistrictWuhanHubei 430299China Department of Respiratory and Critical Care Medicinethe First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Department of Rheumatology and Immunologythe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingJiangsu 210008China Huadong Medical Institute of BiotechniquesNanjingJiangsu 210028China Jiangsu Key Lab of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingJiangsu 211166China. 

出 版 物：《The Journal of Biomedical Research》 (生物医学研究杂志（英文版）)

年 卷 期：2023年第37卷第3期

页      面：166-178页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学] 

基　　金：supported by the Jiangsu Provincial Key Research and Development Program (Grant No.BE2020616) the National Key R&D Program of China (Grant No.2018YFC1200603) the National Science and Technology Major Project (Grant No.2019SWAQ05-5-4) Jiangsu Key Lab of Cancer Biomarkers,Prevention and Treatment,Collaborative Innovation Center for Cancer Personalized Medicine,Nanjing Medical University 

主　　题：SARS-CoV-2 neutralizing antibody single B cell BCR sequencing molecular modeling 

摘      要：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 *** are drugs preferentially used in infectious diseases and are easy to get from immunized *** 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 *** 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 *** 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.