G-quadruplexes (G4s) are non-canonical nucleic acids secondary structures that form within guanine-rich strands of regulatory genomic regions. G4s have been extensively described in the human genome, especially in telomeres and oncogene promoters; in recent years the presence of G4s in viruses has attracted increasing interest. Indeed, G4s have been reported in several viruses, including those involved in recent epidemics, such as the Zika and Ebola viruses. Viral G4s are usually located in regulatory regions of the genome and implicated in the control of key viral processes; in some cases, they have been involved also in viral latency. In this context, G4 ligands have been developed and tested both as tools to study the complexity of G4-mediated mechanisms in the viral life cycle, and as therapeutic agents. In general, G4 ligands showed promising antiviral activity, with G4-mediated mechanisms of action both at the genome and transcript level. This review aims to provide an updated close-up of the literature on G4s in viruses. The current state of the art of G4 ligands in antiviral research is also reported, with particular focus on the structural and physicochemical requirements for optimal biological activity. The achievements and the to-dos in the field are discussed.

中文翻译：

---

G-四链体和 G-四链体配体：抗病毒治疗的靶点和工具

G-四链体 (G4s) 是在调控基因组区域的富含鸟嘌呤的链内形成的非规范核酸二级结构。G4 已在人类基因组中被广泛描述，特别是在端粒和癌基因启动子中；近年来，病毒中 G4s 的存在引起了越来越多的兴趣。事实上，G4s 已在几种病毒中得到报道，包括与最近流行病有关的病毒，如寨卡病毒和埃博拉病毒。病毒 G4 通常位于基因组的调控区域，并与关键病毒过程的控制有关；在某些情况下，它们还涉及病毒潜伏期。在这种情况下，G4 配体已被开发和测试，既可以作为研究病毒生命周期中 G4 介导机制复杂性的工具，也可以作为治疗剂。一般来说，G4 配体显示出有希望的抗病毒活性，在基因组和转录水平上均具有 G4 介导的作用机制。本综述旨在提供有关病毒中 G4 的最新文献特写。还报道了 G4 配体在抗病毒研究中的最新进展，特别关注最佳生物活性的结构和物理化学要求。讨论了该领域的成就和待办事项。