Novel Affibody Molecules Specifically Bind to SARS-CoV-2 Spike Protein and Efficiently Neutralize Delta and Omicron Variants

doi:10.1128/spectrum.03562-22

科研成果详情

题名	Novel Affibody Molecules Specifically Bind to SARS-CoV-2 Spike Protein and Efficiently Neutralize Delta and Omicron Variants
作者	Du, Wangqi1; Jiang, Peipei1,2; Li, Qingfeng 1; Wen, He1; Zheng, Maolin1; Zhang, Jing1; Guo, Yanru 1; Yang, Jia1; Feng, Weixu 1; Ye, Sisi 2; Kamara, Saidu 1; Jiang, Pengfei1; Chen, Jun1; Li, Wenshu1; Zhu, Shanli1; Zhang, Lifang1
发表日期	2023-02-14
发表期刊	MICROBIOLOGY SPECTRUM 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access ; Journal Article
关键词	severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 S protein affibody neutralization SPR receptor binding motif RBM fusion peptide FP
其他关键词	VACCINE ; IMMUNITY
摘要	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been an unprecedented public health disaster in human history, and its spike (S) protein is the major target for vaccines and antiviral drug development. Although widespread vaccination has been well established, the viral gene is prone to rapid mutation, resulting in multiple global spread waves. Therefore, specific antivirals are needed urgently, especially those against variants. In this study, the domain of the receptor binding motif (RBM) and fusion peptide (FP) (amino acids [aa] 436 to 829; denoted RBMFP) of the SARS-CoV-2 S protein was expressed as a recombinant RBMFP protein in Escherichia coii and identified as being immunogenic and antigenically active. Then, the RBMFP proteins were used for phage display to screen the novel affibody. After prokaryotic expression and selection, four novel affibody molecules (Z14, Z149, Z171, and Z327) were obtained. Through surface plasmon resonance (SPR) and pseudovirus neutralization assay, we showed that affibody molecules specifically bind to the RBMFP protein with high affinity and neutralize against SARS-CoV-2 pseudovirus infection. Especially, Z14 and Z171 displayed strong neutralizing activities against Delta and Omicron variants. Molecular docking predicted that affibody molecule interaction sites with RBM overlapped with ACE2. Thus, the novel affibody molecules could be further developed as specific neutralization agents against SARS-CoV-2 variants. IMPORTANCE SARS-CoV-2 and its variants are threatening the whole world. Although a full dose of vaccine injection showed great preventive effects and monoclonal antibody reagents have also been used for a specific treatment, the global pandemic persists. So, developing new vaccines and specific agents are needed urgently. In this work, we expressed the recombinant RBMFP protein as an antigen, identified its antigenicity, and used it as an antigen for affibody phage-display selection. After the prokaryotic expression, the specific affibody molecules were obtained and tested for pseudovirus neutralization. Results showed that the serum antibody induced by RBMFP neutralized Omicron variants. The screened affibody molecules specifically bound the RBMFP of SARS-CoV-2 with high affinity and neutralized the Delta and Omicron pseudovirus in vitro. So, the RBMFP induced serum provides neutralizing effects against pseudovirus in vitro, and the affibodies have the potential to be developed into specific prophylactic agents for SARSCoV-2 and its variants.
出版者	AMER SOC MICROBIOLOGY
出版地	WASHINGTON
ISSN	2165-0497
卷号	11 期号:1 页码:e0356222
DOI	10.1128/spectrum.03562-22
页数	17
WOS类目	Microbiology
WOS研究方向	Microbiology
WOS记录号	WOS:000897894500001
收录类别	SCIE ; PUBMED ; SCOPUS
在线发表日期	2022-12
URL	查看原文
PubMed ID	36511681
SCOPUSEID	2-s2.0-85148113774
通讯作者地址	[Zhu, Shanli]Institute of Molecular Virology and Immunology,Department of Microbiology and Immunology,School of Basic Medical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China ; [Zhang, Lifang]Institute of Molecular Virology and Immunology,Department of Microbiology and Immunology,School of Basic Medical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China
Scopus学科分类	Physiology;Ecology;Immunology and Microbiology (all);Genetics;Microbiology (medical);Cell Biology;Infectious Diseases
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/172023
专题	基础医学院（机能实验教学中心）_病原生物学与免疫学系附属第一医院
通讯作者	Zhu, Shanli; Zhang, Lifang
作者单位	1.Institute of Molecular Virology and Immunology,Department of Microbiology and Immunology,School of Basic Medical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China; 2.The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China
第一作者单位	基础医学院（机能实验教学中心）_病原生物学与免疫学系
通讯作者单位	基础医学院（机能实验教学中心）_病原生物学与免疫学系
第一作者的第一单位	基础医学院（机能实验教学中心）_病原生物学与免疫学系
推荐引用方式 GB/T 7714	Du, Wangqi,Jiang, Peipei,Li, Qingfeng,et al. Novel Affibody Molecules Specifically Bind to SARS-CoV-2 Spike Protein and Efficiently Neutralize Delta and Omicron Variants[J]. MICROBIOLOGY SPECTRUM,2023,11(1):e0356222.
APA	Du, Wangqi., Jiang, Peipei., Li, Qingfeng., Wen, He., Zheng, Maolin., ... & Zhang, Lifang. (2023). Novel Affibody Molecules Specifically Bind to SARS-CoV-2 Spike Protein and Efficiently Neutralize Delta and Omicron Variants. MICROBIOLOGY SPECTRUM, 11(1), e0356222.
MLA	Du, Wangqi,et al."Novel Affibody Molecules Specifically Bind to SARS-CoV-2 Spike Protein and Efficiently Neutralize Delta and Omicron Variants".MICROBIOLOGY SPECTRUM 11.1(2023):e0356222.