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2-脱氧糖核苷衍生物对蜱传脑炎病毒的抗病毒活性。

Antiviral Activity of Uridine Derivatives of 2-Deoxy Sugars against Tick-Borne Encephalitis Virus.

机构信息

Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdansk, Poland.

Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry, Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, Poland.

出版信息

Molecules. 2019 Mar 21;24(6):1129. doi: 10.3390/molecules24061129.

Abstract

Tick-borne encephalitis virus (TBEV) is a causative agent of tick-borne encephalitis (TBE), one of the most important human infections involving the central nervous system. Although effective vaccines are available on the market, they are recommended only in endemic areas. Despite many attempts, there are still no specific antiviral therapies for TBEV treatment. Previously, we synthesized a series of uridine derivatives of 2-deoxy sugars and proved that some compounds show antiviral activity against viruses from the Flaviviridae and Orthomyxoviridae families targeting the late steps of the -glycosylation process, affecting the maturation of viral proteins. In this study, we evaluated a series of uridine derivatives of 2-deoxy sugars for their antiviral properties against two strains of the tick-borne encephalitis virus; the highly virulent TBEV strain Hypr and the less virulent strain Neudoerfl. Four compounds (, , , and ) showed significant anti-TBEV activity with IC values ranging from 1.4 to 10.2 µM and low cytotoxicity. The obtained results indicate that glycosylation inhibitors, which may interact with glycosylated membrane TBEV E and prM proteins, might be promising candidates for future antiviral therapies against TBEV.

摘要

蜱传脑炎病毒(TBEV)是蜱传脑炎(TBE)的病原体,是涉及中枢神经系统的最重要的人类感染之一。尽管市场上有有效的疫苗,但它们仅在流行地区推荐使用。尽管进行了许多尝试,但目前仍没有针对 TBEV 治疗的特异性抗病毒疗法。先前,我们合成了一系列 2-脱氧糖的尿嘧啶衍生物,并证明一些化合物针对黄病毒科和正粘病毒科的病毒具有抗病毒活性,作用于 -糖基化过程的后期步骤,影响病毒蛋白的成熟。在这项研究中,我们评估了一系列 2-脱氧糖的尿嘧啶衍生物对两种蜱传脑炎病毒株(高度毒力的 TBEV 株 Hypr 和毒力较低的 Neudoerfl 株)的抗病毒特性。四种化合物(、、、和)表现出显著的抗 TBEV 活性,IC 值范围为 1.4 至 10.2 μM,细胞毒性低。所得结果表明,糖基化抑制剂可能与糖基化的膜 TBEV E 和 prM 蛋白相互作用,可能成为针对 TBEV 的未来抗病毒治疗的有前途的候选物。

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