作为SARS-CoV-2 Papain-like蛋白酶抑制剂的基于他类的类药物:在Silico和体外研究中

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Raiane Dandara Pereira Pimentel¹, Priscila Goes Camargo², Pedro Henrique R de A Azevedo³

¹Federal University of Rio de Janeiro, CCMN, Chemistry Institute, Postgraduate Program in Chemistry - PGQu, Rio de Janeiro, RJ, 21941-853, Brazil.

Scientific reports

|July 20, 2025

概括

基于他的化合物显示出作为SARS-CoV-2帕帕因类蛋白酶 (PLpro) 抑制剂的前景. 化合物426和432在体外表现出显著的抑制,与GRL-0617相比,具有有利的ADMET配置文件.

科学领域:

生物化学生物化学
计算化学的计算化学
药物发现药物发现药物发现

背景情况:

SARS-CoV-2 帕帕因样蛋白酶 (PLpro) 是抗病毒开发的关键目标.
基于他的类药物为蛋白酶抑制提供了一个新的结构类.

研究的目的:

评估以他为基础的类药物作为SARS-CoV-2的潜在抑制剂.
用计算和实验方法研究它们的结合方式,稳定性和药理动力学特性.

主要方法:

在式方法:分子对接,分子动态模拟,主要组件分析 (PCA),自由能量景观 (FEL) 分析和ADMET预测.
在体外酶测试以确定抑制活性 (IC50值).

主要成果:

五种基于他类药物的化合物 (LQMed 426, 428, 430, 431, 432) 与PLpro活性和全位的相互作用显示出有希望的结果.
化合物426和432在体外表现出强烈的抑制作用 (IC50:分别为0.85微米和1.46微米),与参考抑制剂GRL-0617相当.
分子动力学模拟表明了潜在的全抑制和复合体之间的不同形态稳定性,其中432是最稳定的.
与GRL-0617.7相比,in silico ADMET预测表明这些化合物的安全性概况较为有利.

结论:

基于他的类药物,特别是426和432化合物,是SARS-CoV-2PLpro.pro的有效抑制剂.
这些化合物可能通过非竞争性或混合抑制机制起作用.
它们有前途的疗效和安全性配置将它们定位为新型COVID-19抗病毒药物开发的潜在候选人.

关键词:

这就是COVID-19的原因.抑制剂抑制剂抑制剂分子对接分子对接分子动力学分子动力学 PLpro PLpro 是一个专业的陈类药物陈类药物

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