Integrated Exploration of Pyranocoumarin Derivatives as Synergistic Inhibitors of Dual-target for Mpro and PLpro Proteins of SARS-CoV-2 through Molecular Docking, ADMET Analysis, and Molecular Dynamics Simulation.

IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Imane Yamari, Lamiae El Bouamri, Oussama Abchir, Mohammed Bouachrine, Mhammed El Kouali, Abdelouahid Samadi, Samir Chtita
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Abstract

Aims: This study aimed to explore the potential of natural anticoagulant compounds as synergistic inhibitors of the main protease (Mpro) and papain-like protease (PLpro) of SARS-CoV-2 and find effective therapies against SARS-CoV-2 by investigating the inhibitory effects of natural anticoagulant compounds on key viral proteases.

Objective: The objectives of this study were to conduct rigorous virtual screening and molecular docking analyses to evaluate the binding affinities and interactions of selected anticoagulant compounds with Mpro and PLpro, to assess the pharmacokinetic and pharmacodynamic profiles of the compounds to determine their viability for therapeutic use, and to employ molecular dynamics simulations to understand the stability of the identified compounds over time.

Methods: In this study, a curated collection of natural anticoagulant compounds was conducted. Virtual screening and molecular docking analyses were performed to assess binding affinities and interactions with Mpro and PLpro. Furthermore, pharmacokinetic and pharmacodynamic analyses were carried out to evaluate absorption, distribution, metabolism, and excretion profiles. Molecular dynamics simulations were performed to elucidate compound stability.

Results: Natural compounds exhibiting significant inhibitory activity against Mpro and PLpro were identified. A dual-target approach was established as a promising strategy for attenuating viral replication and addressing coagulopathic complications associated with SARS-CoV-2 infection.

Conclusion: The study lays a solid foundation for experimental validation and optimization of identified compounds, potentially leading to the development of precise treatments for SARS-CoV-2.

通过分子对接、ADMET分析和分子动力学模拟综合探索吡喃香豆素衍生物作为SARS-CoV-2的Mpro和PLpro蛋白双靶标协同抑制剂
目的:本研究旨在探索天然抗凝剂化合物作为SARS-CoV-2主要蛋白酶(Mpro)和木瓜蛋白酶(PLpro)协同抑制剂的潜力,并通过研究天然抗凝剂化合物对关键病毒蛋白酶的抑制作用,找到抗击SARS-CoV-2的有效疗法:本研究的目的是进行严格的虚拟筛选和分子对接分析,以评估选定的抗凝剂化合物与Mpro和PLpro的结合亲和力和相互作用,评估化合物的药代动力学和药效学特征,以确定其治疗用途的可行性,并采用分子动力学模拟来了解已鉴定化合物的长期稳定性:本研究收集了一系列天然抗凝化合物。进行了虚拟筛选和分子对接分析,以评估与 Mpro 和 PLpro 的结合亲和力和相互作用。此外,还进行了药代动力学和药效学分析,以评估吸收、分布、代谢和排泄情况。还进行了分子动力学模拟,以阐明化合物的稳定性:结果:发现了对 Mpro 和 PLpro 具有明显抑制活性的天然化合物。双靶点方法被认为是一种很有前途的策略,既能抑制病毒复制,又能解决与 SARS-CoV-2 感染相关的凝血病理并发症:结论:这项研究为已鉴定化合物的实验验证和优化奠定了坚实的基础,有望开发出治疗 SARS-CoV-2 的精确疗法。
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来源期刊
Current medicinal chemistry
Current medicinal chemistry 医学-生化与分子生物学
CiteScore
8.60
自引率
2.40%
发文量
468
审稿时长
3 months
期刊介绍: Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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