Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9747 AG, Groningen, The Netherlands.
Department of Environmental Science, Aarhus University, 4000, Roskilde, Denmark.
Cell Mol Life Sci. 2021 Apr;78(8):3921-3940. doi: 10.1007/s00018-021-03759-0. Epub 2021 Feb 2.
The emergence and re-emergence of viral epidemics and the risks of antiviral drug resistance are a serious threat to global public health. New options to supplement or replace currently used drugs for antiviral therapy are urgently needed. The research in the field of ribosomally synthesized and post-translationally modified peptides (RiPPs) has been booming in the last few decades, in particular in view of their strong antimicrobial activities and high stability. The RiPPs with antiviral activity, especially those against enveloped viruses, are now also gaining more interest. RiPPs have a number of advantages over small molecule drugs in terms of specificity and affinity for targets, and over protein-based drugs in terms of cellular penetrability, stability and size. Moreover, the great engineering potential of RiPPs provides an efficient way to optimize them as potent antiviral drugs candidates. These intrinsic advantages underscore the good therapeutic prospects of RiPPs in viral treatment. With the aim to highlight the underrated antiviral potential of RiPPs and explore their development as antiviral drugs, we review the current literature describing the antiviral activities and mechanisms of action of RiPPs, discussing the ongoing efforts to improve their antiviral potential and demonstrate their suitability as antiviral therapeutics. We propose that antiviral RiPPs may overcome the limits of peptide-based antiviral therapy, providing an innovative option for the treatment of viral disease.
病毒流行病的出现和再现以及抗病毒药物耐药性的风险是对全球公共卫生的严重威胁。迫切需要新的选择来补充或替代目前用于抗病毒治疗的药物。在核糖体合成和翻译后修饰肽（RiPPs）领域的研究在过去几十年中蓬勃发展，特别是考虑到它们强大的抗菌活性和高稳定性。具有抗病毒活性的 RiPPs，特别是针对包膜病毒的 RiPPs，现在也越来越受到关注。与小分子药物相比，RiPPs 在针对靶点的特异性和亲和力方面具有优势，与基于蛋白质的药物相比，在细胞通透性、稳定性和大小方面具有优势。此外，RiPPs 的巨大工程潜力为将其优化为有效的抗病毒药物提供了一种有效的方法。这些内在优势突出了 RiPPs 在病毒治疗中的良好治疗前景。为了强调 RiPPs 被低估的抗病毒潜力并探索其作为抗病毒药物的开发，我们回顾了描述 RiPPs 的抗病毒活性和作用机制的现有文献，讨论了提高其抗病毒潜力的正在进行的努力，并证明了它们作为抗病毒治疗药物的适用性。我们提出，抗病毒 RiPPs 可能克服基于肽的抗病毒治疗的局限性，为病毒疾病的治疗提供一种创新的选择。
