A potent neutralizing nanobody targeting a unique epitope on the receptor-binding domain of SARS-CoV-2 spike protein

Zhang，Yuting1; Wang，Dan2; Xiang，Qi3; Hu，Xiaohui1; Zhang，Yuting4; Wu，Lijie5; Zhang，Zhaoyong6; Wang，Yanqun6; Zhao，Jincun7; McCormick，Peter J.8; Fu，Jinheng9; Fu，Yang3; Zhang，Jin1; Jiang，Haihai1; Li，Jian10

2024

10.1016/j.virol.2023.109925

Virology   影响因子和分区

0042-6822

1096-0341

SARS-CoV-2 and its variants continue to threaten public health. Nanobodies that block the attachment of the RBD to host cell angiotensin-converting enzyme 2 (ACE2) represent promising drug candidates. In this study, we reported the identification and structural biological characterization of a nanobody from a RBD-immunized alpaca. The nanobody, termed as 2S-1-19, shows outstanding neutralizing activity against both pseudotyped and authentic SARS-CoV-2 viruses. The crystal structure of 2S-1-19 bound to SARS-CoV-2 RBD reveals an epitope that overlaps with the binding site for ACE2. We also showed that 2S-1-19 reserves promising, though compromised, neutralizing activity against the Delta variant and that the trivalent form of 2S-1-19 remarkably increases its neutralizing capacity. Despite this, neither the monomeric or trimeric 2S-1-19 could neutralize the Omicron BA.1.1 variant, possibility due to the E484A and Q493K mutations found within this virus variant. These data provide insights into immune evasion caused by SARS-CoV-2 variants.

Crystal structure Nanobody RBD SARS-CoV-2 Trimerization

SCI

英语

其他

MICROBIOLOGY

2-s2.0-85180007301

Scopus

1.School of Basic Medical Sciences,Nanchang University,Nanchang,330031,China
2.Key Lab for Agro-product Processing and Quality Control of Nanchang City,College of Food Science and Engineering,Jiangxi Agricultural University,Nanchang,330045,China
3.School of Medicine,Southern University of Science and Technology,Shenzhen,518055,China
4.Shenzhen Crystalo Biopharmaceutical Co.,Ltd,Shenzhen,518118,China
5.IHuman Institute,ShanghaiTech University,201210,China
6.State Key Laboratory of Respiratory Disease,National Clinical Research Centre for Respiratory Disease,Guangzhou Institute of Respiratory Health,First Affiliated Hospital of Guangzhou Medical University,Guangzhou,511436,China
7.State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 511436, China; Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510060, China; Guangzhou Laboratory, Bio-island, Guangzhou, Guangdong, 510320, China; Shanghai Institute for Advanced Immunochemical Studies, School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China
8.William Harvey Research Institute,Bart's and the London School of Medicine and Dentistry,Queen Mary University of London,London,EC1M 6BQ,United Kingdom
9.Jiangxi-OAI Joint Research Institution,Nanchang University,Nanchang,330047,China
10.College of Pharmaceutical Sciences,Gannan Medical University,341000,China

Zhang，Yuting,Wang，Dan,Xiang，Qi,et al. A potent neutralizing nanobody targeting a unique epitope on the receptor-binding domain of SARS-CoV-2 spike protein[J]. Virology,2024,589.

Zhang，Yuting.,Wang，Dan.,Xiang，Qi.,Hu，Xiaohui.,Zhang，Yuting.,...&Li，Jian.(2024).A potent neutralizing nanobody targeting a unique epitope on the receptor-binding domain of SARS-CoV-2 spike protein.Virology,589.

Zhang，Yuting,et al."A potent neutralizing nanobody targeting a unique epitope on the receptor-binding domain of SARS-CoV-2 spike protein".Virology 589(2024).