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加利迪塞维尔三酸盐促进了登革热-2病毒聚合酶在结合之前立即停滞

Sandesh Deshpande¹, Wenjuan Huo¹, Rinu Shrestha^2,3

¹School of Biological Sciences, University of Auckland, Auckland 1010, New Zealand.

ACS infectious diseases

|July 24, 2023

概括

加利迪西维三酸盐抑制登革热和寨卡病毒聚合酶,但不会导致延迟RNA合成终止. 它被纳入病毒RNA是低效的,这表明登革热复制减弱的替代机制.

科学领域:

病毒学病毒学
药物发现药物发现药物发现

背景情况:

登革热和寨卡病毒对全球健康造成重大负担.
加利迪西维尔 (galidesivir) 是一种核糖类相似物,正在研究其对抗黄病毒病毒的抗病毒特性.
以前的研究表明,加利迪西维尔可能通过终止RNA合成来抑制病毒复制.

研究的目的:

直接调查Galidesivir三酸盐对登革热-2和寨卡病毒RNA聚合酶活性的体外影响.
为了确定Galidesivir三酸盐是否导致RNA合成的延迟终止.

主要方法:

加利迪西维尔三酸盐的化学合成.
使用二核酸原料RNA合成在多元 (U) 模板上的抑制试验.
RNA原始延伸试验分析聚合酶停滞和核酸结合.

主要成果:

加利迪西维尔三酸盐显示出对登革热-2和寨卡聚合酶 (IC50值~42-47μM) 的同强抑制.
登革热-2聚合酶在试图结合加利迪西维尔时陷入停滞,产生截断的RNA.
加利迪西维尔被纳入效率低下,并没有始终导致延迟链终结,观察到全长RNA合成.
由于模板序列的影响,连续纳入加利迪西维尔被推翻了.

结论:

延迟RNA合成终止的拟议机制可能不能完全解释Galidesivir减弱登革热复制的作用.
加利迪西维尔的抗病毒活性可能涉及除了简单的链终结之外的其他机制.
模板依赖的整合效率影响了Galidesivir的抑制作用.

关键词:

弗拉维病毒 (flavivirus) 是一种病毒.这是一种依赖RNA的RNA聚合酶.在SYTO 9中,有9个类型.这是一种抗病毒药物.核酸类比的核酸类比

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