Zhihong Wang, Zhuangzhuang Shi, Xiaochen Liao, Guiqi Quan, Hui Dong, Pinnan Zhao, Yangyihua Zhou, Ning Shi, Jie Wang, Yahui Wu, Chunxia Qiao, Xin Ying Li, Ran Zhang, Zekun Wang, Tiecheng Wang, Xiang Gao, Jiannan Feng, Longlong Luo
{"title":"Broad-Spectrum Engineered Multivalent Nanobodies Against SARS-CoV-1/2.","authors":"Zhihong Wang, Zhuangzhuang Shi, Xiaochen Liao, Guiqi Quan, Hui Dong, Pinnan Zhao, Yangyihua Zhou, Ning Shi, Jie Wang, Yahui Wu, Chunxia Qiao, Xin Ying Li, Ran Zhang, Zekun Wang, Tiecheng Wang, Xiang Gao, Jiannan Feng, Longlong Luo","doi":"10.1002/advs.202402975","DOIUrl":null,"url":null,"abstract":"<p><p>SARS-CoV-2 Omicron sublineages escape most preclinical/clinical neutralizing antibodies in development, suggesting that previously employed antibody screening strategies are not well suited to counteract the rapid mutation of SARS-CoV-2. Therefore, there is an urgent need to screen better broad-spectrum neutralizing antibody. In this study, a comprehensive approach to design broad-spectrum inhibitors against both SARS-CoV-1 and SARS-CoV-2 by leveraging the structural diversity of nanobodies is proposed. This includes the de novo design of a fully human nanobody library and the camel immunization-based nanobody library, both targeting conserved epitopes, as well as the development of multivalent nanobodies that bind nonoverlapping epitopes. The results show that trivale B11-E8-F3, three nanobodies joined tandemly in trivalent form, have the broadest spectrum and efficient neutralization activity, which spans from SARS-CoV-1 to SARS-CoV-2 variants. It is also demonstrated that B11-E8-F3 has a very prominent preventive and some therapeutic effect in animal models of three authentic viruses. Therefore, B11-E8-F3 has an outstanding advantage in preventing SARS-CoV-1/SARS-CoV-2 infections, especially in immunocompromised populations or elderly people with high-risk comorbidities.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":null,"pages":null},"PeriodicalIF":14.3000,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Science","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1002/advs.202402975","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
SARS-CoV-2 Omicron sublineages escape most preclinical/clinical neutralizing antibodies in development, suggesting that previously employed antibody screening strategies are not well suited to counteract the rapid mutation of SARS-CoV-2. Therefore, there is an urgent need to screen better broad-spectrum neutralizing antibody. In this study, a comprehensive approach to design broad-spectrum inhibitors against both SARS-CoV-1 and SARS-CoV-2 by leveraging the structural diversity of nanobodies is proposed. This includes the de novo design of a fully human nanobody library and the camel immunization-based nanobody library, both targeting conserved epitopes, as well as the development of multivalent nanobodies that bind nonoverlapping epitopes. The results show that trivale B11-E8-F3, three nanobodies joined tandemly in trivalent form, have the broadest spectrum and efficient neutralization activity, which spans from SARS-CoV-1 to SARS-CoV-2 variants. It is also demonstrated that B11-E8-F3 has a very prominent preventive and some therapeutic effect in animal models of three authentic viruses. Therefore, B11-E8-F3 has an outstanding advantage in preventing SARS-CoV-1/SARS-CoV-2 infections, especially in immunocompromised populations or elderly people with high-risk comorbidities.
期刊介绍:
Advanced Science is a prestigious open access journal that focuses on interdisciplinary research in materials science, physics, chemistry, medical and life sciences, and engineering. The journal aims to promote cutting-edge research by employing a rigorous and impartial review process. It is committed to presenting research articles with the highest quality production standards, ensuring maximum accessibility of top scientific findings. With its vibrant and innovative publication platform, Advanced Science seeks to revolutionize the dissemination and organization of scientific knowledge.