Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, USA.
Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN, USA.
J Nanobiotechnology. 2024 May 31;22(1):304. doi: 10.1186/s12951-024-02573-7.
Nanobodies, single-domain antibodies derived from variable domain of camelid or shark heavy-chain antibodies, have unique properties with small size, strong binding affinity, easy construction in versatile formats, high neutralizing activity, protective efficacy, and manufactural capacity on a large-scale. Nanobodies have been arisen as an effective research tool for development of nanobiotechnologies with a variety of applications. Three highly pathogenic coronaviruses (CoVs), SARS-CoV-2, SARS-CoV, and MERS-CoV, have caused serious outbreaks or a global pandemic, and continue to post a threat to public health worldwide. The viral spike (S) protein and its cognate receptor-binding domain (RBD), which initiate viral entry and play a critical role in virus pathogenesis, are important therapeutic targets. This review describes pathogenic human CoVs, including viral structures and proteins, and S protein-mediated viral entry process. It also summarizes recent advances in development of nanobodies targeting these CoVs, focusing on those targeting the S protein and RBD. Finally, we discuss potential strategies to improve the efficacy of nanobodies against emerging SARS-CoV-2 variants and other CoVs with pandemic potential. It will provide important information for rational design and evaluation of therapeutic agents against emerging and reemerging pathogens.
纳米抗体，即源自骆驼科或鲨鱼重链抗体可变区的单域抗体，具有体积小、结合亲和力强、易于构建多种形式、中和活性高、保护效力高、大规模生产能力等独特性质。纳米抗体已成为开发纳米生物技术的有效研究工具，具有多种应用。三种高致病性冠状病毒（CoV），即 SARS-CoV-2、SARS-CoV 和 MERS-CoV，已造成严重爆发或全球大流行，并继续对全球公共卫生构成威胁。病毒刺突（S）蛋白及其同源受体结合域（RBD），启动病毒进入并在病毒发病机制中发挥关键作用，是重要的治疗靶点。本综述描述了致病性人类 CoV，包括病毒结构和蛋白，以及 S 蛋白介导的病毒进入过程。还总结了针对这些 CoV 的纳米抗体的最新进展，重点介绍了针对 S 蛋白和 RBD 的纳米抗体。最后，我们讨论了提高针对新兴 SARS-CoV-2 变体和其他具有大流行潜力的 CoV 的纳米抗体疗效的潜在策略。它将为针对新发和再发病原体的治疗剂的合理设计和评估提供重要信息。
