Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Parque Tecnológico de Ciencias de la Salud, Granada, Spain.
J Viral Hepat. 2013 Feb;20(2):103-12. doi: 10.1111/j.1365-2893.2012.01629.x. Epub 2012 Jul 17.
The RNA genome of hepatitis C virus (HCV) contains multiple conserved structural RNA domains that play key roles in essential viral processes. A conserved structural component within the 3' end of the region coding for viral RNA-dependent RNA polymerase (NS5B) has been characterized as a functional cis-acting replication element (CRE). This study reports the ability of two RNA aptamers, P-58 and P-78, to interfere with HCV replication by targeting the essential 5BSL3.2 domain within this CRE. Structure-probing assays showed the binding of the aptamers to the CRE results in a structural reorganization of the apical portion of the 5BSL3.2 stem-loop domain. This interfered with the binding of the NS5B protein to the CRE and induced a significant reduction in HCV replication (≈50%) in an autonomous subgenomic HCV replication system. These results highlight the potential of this CRE as a target for the development of anti-HCV therapies and underscore the potential of antiviral agents based on RNA aptamer molecules.
丙型肝炎病毒 (HCV) 的 RNA 基因组包含多个保守的结构 RNA 结构域，这些结构域在病毒的基本过程中发挥关键作用。编码 HCV RNA 依赖性 RNA 聚合酶 (NS5B) 的区域 3' 末端的保守结构元件已被鉴定为具有功能的顺式作用复制元件 (CRE)。本研究报告了两种 RNA 适体，P-58 和 P-78，通过靶向该 CRE 内的必需 5BSL3.2 结构域，干扰 HCV 复制的能力。结构探测实验表明，适体与 CRE 的结合导致 5BSL3.2 茎环结构域顶端部分的结构重排。这干扰了 NS5B 蛋白与 CRE 的结合，并在自主亚基因组 HCV 复制系统中诱导 HCV 复制显著减少（约 50%）。这些结果突出了该 CRE 作为抗 HCV 治疗开发的靶标，强调了基于 RNA 适体分子的抗病毒药物的潜力。
