CY Cergy Paris Université, CNRS, BioCIS, 95000 Cergy Pontoise, France; Université Paris-Saclay, CNRS, BioCIS, 92290 Châtenay-Malabry, France.
Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdansk, Poland.
Bioorg Med Chem. 2022 Aug 15;68:116858. doi: 10.1016/j.bmc.2022.116858. Epub 2022 May 29.
Ribavirin is an unnatural nucleoside exhibiting broad spectrum of antiviral and antitumor activities, still very widely studied particularly in a repositioning approach. C-triazolyl nucleoside analogues of ribavirin have been synthesized, as well as prodrugs and glycosylated or peptide conjugates to allow a better activity by vectorization into the liver or by facilitating uptake into the cells. The antiviral properties of all synthesized compounds have been evaluated in vitro against two important human viral pathogens belonging to the Flaviviridae family: hepatitis C virus (HCV) and Zika virus (ZIKV). There are no therapeutic options for Zika virus, whereas those available for HCV can be still improved. Our results indicated that compound 2 carrying an N-hydroxy carboxamide function exhibits the most inhibitory activities against both viruses. This compound moderately inhibited the propagation of HCV with an IC value of 49.1 μM and Zika virus with an IC of 33.2 μM comparable to ribavirin in the Vero cell line. The results suggest that compound 2 and its new derivatives may be candidates for further development of new anti-HCV and anti-ZIKV antiviral drugs.
利巴韦林是一种具有广谱抗病毒和抗肿瘤活性的非天然核苷，仍在广泛研究中，特别是在重新定位方法方面。已经合成了利巴韦林的 C-三唑核苷类似物，以及前药和糖基化或肽缀合物，以通过向肝脏的载体化或通过促进细胞摄取来提高活性。所有合成化合物的抗病毒特性都已在体外针对属于黄病毒科的两种重要人类病毒病原体进行了评估：丙型肝炎病毒（HCV）和寨卡病毒（ZIKV）。目前尚无针对寨卡病毒的治疗方法，而针对 HCV 的治疗方法仍有待改进。我们的研究结果表明，带有 N-羟基羧酰胺功能的化合物 2 对这两种病毒均表现出最强的抑制活性。该化合物适度抑制 HCV 的增殖，IC 值为 49.1 μM，Zika 病毒的 IC 值为 33.2 μM，在 Vero 细胞系中与利巴韦林相当。这些结果表明，化合物 2 及其新衍生物可能是进一步开发新型抗 HCV 和抗 ZIKV 抗病毒药物的候选药物。
