Abstract:

The biomedical applications of viruses have attracted the attention of researchers because of their unique properties such as excellent dispersion, stable structure, and mass production. At present, most of viruses for such a purpose need to be assembled with different functional components including fluorescent probes, targeting ligands, therapeutic molecules, and so on, to endow them with required performance, for example, visualization, immune compatibility, specific targeting, and others. Before integrating the viruses with these functional components, they must be modified. The structure of enveloped viruses consists of nucleic acid, capsid, and envelope. Therefore, biological macromolecules such as proteins, polysaccharides, phospholipids, and nucleic acids can all be used as targets for the structural modification of the viruses. The viral protein component can be derivatized and functionalized genetically or post-translationally. For example, functional proteins or peptides can be genetically fused with the viral capsid directly. However, the other biomolecules including glycans, lipids, nucleic acids, and various metabolites are not amenable as such genetically encoded tags. Bioorthogonal reactions through which the compatible reactive groups can selectively conjugate with each other under physiological conditions, and also they are not toxic to cells and organisms. The major features of these reactions include: outstanding reliability, specific selectivity, and good compatibility with naturally occurring functional groups, making them a powerful tool for studying the structure and function of viruses.In this article, major characteristics of these bioorthogonal reactions are summarized. Subsequently, general schemes for bioorthogonal modifications on different viral components are depicted. Furthermore, we review the recent applications of bioorthogonal reactions in virus-related research, including viral tracking, vaccine development, the diagnosis of viral infections, and virus-based delivery systems. Finally, we conclude that based on the structure and application of viruses, researchers could select appropriate bioorthogonal reactions for viruses engineering, and other strategies, such as genetic engineering, biological coupling, and so on, could also be used to modify viruses to expand their applications.

Key words: viruses, bioorthogonal reactions, biological macromolecules, functionalization, biomedical applications

摘要：

病毒具有分散性好、结构规则、可大量复制等特性，使其在生物医学领域的应用日益受到研究者关注。目前大多数基于病毒的生物医学应用主要需要将其与荧光探针、肿瘤识别分子等不同功能元件组装，进而赋予病毒可视化、免疫相容、靶向等性能。对于包膜病毒而言，其结构组成主要包括：包膜、衣壳和核酸。因此，组成病毒的生物大分子（蛋白质、糖类、脂类和核酸），均可作为靶标与不同元件进行可控组装和功能整合。近年来，基于生物正交反应的生物大分子修饰策略已经被广泛应用于病毒不同组分的工程化改造。本文概述了常用于生物大分子修饰的生物正交反应类型与特点，以及生物正交反应对病毒不同组分的改造策略；同时，介绍了病毒功能化在病毒动态示踪、疫苗开发、病毒检测、递送载体构建等领域的研究进展。生物正交反应技术的发展，将推动病毒功能化改造策略的进一步完善，进而拓展病毒的应用方向。

关键词: 病毒, 生物正交反应, 生物大分子, 功能化, 生物医学应用