针对人类 T 型淋巴细胞病毒-1 型的整合酶抑制剂的再利用:一种计算方法。

IF 2.7 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Prashasti Sinha, Anil Kumar Yadav
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引用次数: 0

摘要

成人T细胞淋巴瘤(ATL)是由被称为人类T细胞白血病I型(HTLV-1)的delta逆转录病毒家族成员引起的。由于无法治愈,这项研究的动机是找出一些针对该病毒的再利用药物。为找到治疗 HTLV-1 的药物,一种快速准确的方法是通过化学信息学的药物再利用,对美国食品药物管理局批准的整合酶抗 HTLV-1 感染的抗病毒药物数据集进行分析。为了确定抗病毒药物如何与 HTLV-1 整合酶活性区的重要残基相互作用,我们使用了分子对接建模。配体在活性区内的稳定行为随后通过分子动力学证实了可能的受体-药物复合物。Cabotegravir、Raltegravir和Elvitegravir与目标物的对接得分最高,表明它们能与HTLV-1整合酶紧密结合。此外,MD 模拟显示,Cabotegravir-HTLV-1、Raltegravir-HTLV-1 和 Elvitegravir-HTLV-1 的相互作用是稳定的。很明显,有必要在临床试验和实验测试中对这些药物进行更多测试,以证明它们对HTLV-1感染的疗效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Repurposing integrase inhibitors against human T-lymphotropic virus type-1: a computational approach.

Adult T-cell Lymphoma (ATL) is caused by the delta retrovirus family member known as Human T-cell Leukaemia Type I (HTLV-1). Due to the unavailability of any cure, the study gained motivation to identify some repurposed drugs against the virus. A quick and accurate method of screening licensed medications for finding a treatment for HTLV-1 is by cheminformatics drug repurposing in order to analyze a dataset of FDA approved integrase antivirals against HTLV-1 infection. To determine how the antiviral medications interacted with the important residues in the HTLV-1 integrase active regions, molecular docking modeling was used. The steady behavior of the ligands inside the active region was then confirmed by molecular dynamics for the probable receptor-drug complexes. Cabotegravir, Raltegravir and Elvitegravir had the best docking scores with the target, indicating that they can tightly bind to the HTLV-1 integrase. Moreover, MD simulation revealed that the Cabotegravir-HTLV-1, Raltegravir-HTLV-1 and Elvitegravir-HTLV-1 interactions were stable. It is obvious that more testing of these medicines in both clinical trials and experimental tests is necessary to demonstrate their efficacy against HTLV-1 infection.

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来源期刊
Journal of Biomolecular Structure & Dynamics
Journal of Biomolecular Structure & Dynamics 生物-生化与分子生物学
CiteScore
8.90
自引率
9.10%
发文量
597
审稿时长
2 months
期刊介绍: The Journal of Biomolecular Structure and Dynamics welcomes manuscripts on biological structure, dynamics, interactions and expression. The Journal is one of the leading publications in high end computational science, atomic structural biology, bioinformatics, virtual drug design, genomics and biological networks.
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