Herein, we report, for the first time, the screening of several ligands in terms of their ability to bind and stabilize G-quadruplexes (G4) found in seven human Papillomavirus (HPV) genomes. Using a variety of biophysical assays, HPV G-quadruplexes were shown to possess a high degree of structural polymorphism upon ligand binding, which may have an impact on transcription, replication, and viral protein production. A sequence found in high-risk HPV16 genotype folds into multiple non-canonical DNA structures; it was converted into a major G4 conformation upon interaction with a well-characterized highly selective G4 ligand, PhenDC3, which may have an impact on the viral infection. Likewise, HPV57 and 58, which fold into multiple G4 structures, were found to form single stable complexes in the presence of two other G4 ligands, C₈ and pyridostatin, respectively. In addition, one of the selected compounds, the acridine derivative C₈, demonstrated a significant antiviral effect in HPV18-infected organotypic raft cultures. Altogether, these results indicate that targeting HPV G4s may be an alternative route for the development of novel antiviral therapies.

中文翻译：

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人类乳头瘤病毒富含 G 的区域作为潜在的抗病毒药物靶点

在此，我们首次报告了根据其结合和稳定在七个人乳头瘤病毒 (HPV) 基因组中发现的 G-四链体 (G4) 的能力筛选几种配体。使用各种生物物理测定，HPV G-四链体在配体结合后显示出高度的结构多态性，这可能对转录、复制和病毒蛋白产生产生影响。在高危 HPV16 基因型中发现的一个序列折叠成多个非规范 DNA 结构；它在与表征良好的高选择性 G4 配体 PhenDC3 相互作用后转化为主要的 G4 构象，这可能对病毒感染产生影响。同样，发现折叠成多个 G4 结构的 HPV57 和 58 在其他两种 G4 配体 C₈和吡啶抑制素。此外，选定的化合物之一，吖啶衍生物 C ₈，在 HPV18 感染的器官型筏培养物中显示出显着的抗病毒作用。总之，这些结果表明靶向 HPV G4s 可能是开发新型抗病毒疗法的替代途径。