Identification of a conserved G-quadruplex in E165R of ASFVAfrican swine fever virus (ASFV) is a double-stranded DNA arbovirus with high transmissibility and mortality rates. It has caused immense economic losses to the global pig industry. Currently, no effective vaccines or medications are to combat ASFV infection. G-quadruplex (G4) structures have attracted increasing interest because of their regulatory role in vital biological processes. In this study, we identified a conserved G-rich sequence within the E165R gene of ASFV. Subsequently, using various methods, we verified that this sequence could fold into a parallel G4. In addition, the G4-stabilizers pyridostatin and 5,10,15,20-tetrakis-(N-methyl-4-pyridyl) porphin (TMPyP4) can bind and stabilize this G4 structure, thereby inhibiting E165R gene expression, and the inhibitory effect is associated with G4 formation. Moreover, the G4 ligand pyridostatin substantially impeded ASFV proliferation in Vero cells by reducing gene copy number and viral protein expression. These compelling findings suggest that G4 structures may represent a promising and novel antiviral target against ASFV.

中文翻译：

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鉴定非洲猪瘟病毒 (ASFV) E165R 内保守的 G-四链体作为潜在的抗病毒靶点


ASFVA E165R 中保守 G 四链体的鉴定非洲猪瘟病毒 (ASFV) 是一种双链 DNA 虫媒病毒，具有高传播性和死亡率。给全球养猪业造成了巨大的经济损失。目前，尚无有效的疫苗或药物来对抗非洲猪瘟病毒感染。 G-四链体 (G4) 结构因其在重要生物过程中的调节作用而引起了越来越多的兴趣。在这项研究中，我们鉴定了 ASFV E165R 基因内的一个保守的富含 G 的序列。随后，我们使用各种方法验证了该序列可以折叠成平行的G4。此外，G4稳定剂吡啶他汀和5,10,15,20-四-(N-甲基-4-吡啶基)卟啉(TMPyP4)可以结合并稳定这个G4结构，从而抑制E165R基因表达，并发挥抑制作用与G4形成有关。此外，G4 配体吡啶他汀通过减少基因拷贝数和病毒蛋白表达，显着阻碍了 Vero 细胞中的 ASFV 增殖。这些令人信服的发现表明，G4 结构可能代表一种有前景的新型抗非洲猪瘟病毒靶点。