基于碎片的发现和优化寨卡病毒NS3化酶连接体作为抗病毒攻击候选者

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Updated: Jan 7, 2026

High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication

High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication

Published on: October 30, 2021

Herika D A Vidal¹, Nathalya C M R Mesquita², Ana C B Bernardes¹

¹Centre of Excellence for Research in Sustainable Chemistry, Department of Chemistry, Federal University of São Carlos, 13565-905, São Carlos, SP, Brazil.

European journal of medicinal chemistry

|December 25, 2025

概括

研究人员确定了一种氨酸衍生物,通过向NS3酶来抑制寨卡病毒 (ZIKV) 复制. 这一发现为开发ZIKV抗病毒药物提供了新的分子支架.

科学领域:

病毒学病毒学
药物发现药物发现药物发现
结构生物学结构生物学

背景情况:

寨卡病毒 (ZIKV) 是一种由蚊子传播的黄病毒,缺乏经批准的疫苗或治疗方法.
ZIKV非结构蛋白3酶域 (NS3Hel) 对病毒RNA复制至关重要,也是关键药物标.

研究的目的:

通过高通量晶体学片段查,识别针对ZIKV NS3Hel的新型带.
探索潜在的抗病毒药物开发的结构-活性关系.

主要方法:

在ZIKV NS3Hel.中进行高通量晶体学碎片选.
鉴定出碎片的合成和结构改造.
生物物理和生物化学测定以评估结合亲和力和抗病毒活性.
在ZIKV复制系统中的评估.

主要成果:

鉴定出了四个碎片 (antoin,oxadiazole,phenylurea) 的存在.
在RNA结合部位的入口增加亲和力是很困难的.
一种尿素衍生物在RNA结合部位的退出处显示出较低的微分子亲和力 (Kd = 40 μM).
这种衍生物在ZIKV复制体系统中表现出适度的抑制.

结论:

针对NS3Hel的RNA结合部位退出是ZIKV抑制剂设计的一个有希望的策略.
氨酸部分代表了一种用于开发ZIKV抗病毒药物的新型分子支架.

关键词:

抗病毒药物设计设计在 NS3 螺旋酶.尿素衍生品尿素衍生品 RNA结合部位抑制剂RNA结合部位抑制剂寨卡病毒寨卡病毒寨卡病毒

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