使用西纳皮酸作为对MERS-CoV的抑制性抗病毒剂PLpro
Mudassar Shahid1, Ahmed L Alaofi1, Mushtaq Ahmad Ansari2
1Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
概括
酸 (SA) 有效抑制MERS-CoV PLpro,这是病毒复制中的关键酶. 这种天然化合物显示出作为潜在的治疗剂对中东呼吸综合征冠状病毒 (MERS-CoV) 感染的承诺.
科学领域:
- 生物化学 生化学
- 病毒学 病毒学
- 药理学 药理学是指药理学的学科.
背景情况:
- 冠状病毒,包括MERS-CoV,由于它们的流行病潜力和缺乏有效治疗方法,造成了重大公共卫生风险.
- 帕帕因类蛋白酶 (PLpro) 对于MERS-CoV复制至关重要,使其成为抗病毒药物开发的关键目标.
研究的目的:
- 研究天然植物药物酸 (SA) 的潜力,作为MERS-CoV PLpro.的抑制剂.
- 评估SA与MERS-CoV PLpro.的相互作用,抑制和结合部位.
主要方法:
- 热转换试验 (TSA) 评估药物酶相互作用.
- 酶抑制试验量化SA对MERS-CoV PLpro.的抑制作用.
- 使用Autodock Vina进行分子对接,使用PyMOL和Maestro Schrödinger进行分析,以确定结合部位和效率.
主要成果:
- 酸显示了MERS-CoV PLpro的剂量依赖性抑制,其IC50值为68.58μM.
- 运输安全局表示,SA增加了MERS-CoV PLpro的化温度,这表明直接相互作用.
- 分子对接显示,SA与MERS-CoV PLpro的阻断循环 (BL2) 结合,与特定的氨基酸残留相互作用.
结论:
- 酸对MERS-CoV PLpro.表现出显著的抑制活性.
- SA与MERS-CoV PLpro的相互作用及其已知的抗病毒特性表明它有可能成为MERS-CoV感染的治疗候选者.
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