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使用计算方法探索[具体物质]对登革热病毒NS2B/NS3蛋白酶和NS5聚合酶的抑制潜力。

Exploring the inhibitory potential of against dengue virus NS2B/NS3 protease and NS5 polymerase using computational approaches.

作者信息

Mukhtar Mamuna, Khan Haris Ahmed, Zaidi Najam Us Sahar Sadaf

机构信息

Atta ur Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST) H-12 44000 Islamabad Pakistan

Department of Biotechnology, University of Mianwali 42200 Punjab Pakistan.

出版信息

RSC Adv. 2023 Jun 16;13(27):18306-18322. doi: 10.1039/d3ra02613b. eCollection 2023 Jun 15.


DOI:10.1039/d3ra02613b
PMID:37333789
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10273825/
Abstract

Dengue fever, a highly infectious and rapidly spreading vector borne illness, is classified as a Neglected Tropical Disease (NTD) by WHO because they generally afflict the world's poor and historically have not received as much attention as other diseases. DENV NS2B/NS3 protease and NS5 polymerase are regarded as significant prospective therapeutic targets because of their critical involvement in the viral replication cycle. To date, no specific antiviral agents exist for dengue. The commonly used herbal plant is known for its antibacterial, antiviral, anti-inflammatory, wound-healing, and dermatological properties. Nevertheless, not enough studies on the antiviral effects of against DENV are reported. The current study used several prediction techniques to anticipate the oral bioavailability of substances, druglikeness, and non-toxic and non-mutagenic effects which could lead to the development of novel, safer medications. Therefore, the current study was conducted to explore the inhibitory potential of 18 phytochemicals from against two important enzymes of dengue virus , NS2B/NS3 and NS5. Promising results have been observed for NS2B/NS3 with Taraxerol (-9.1 kcal mol), isoquercetin (8.4 kcal mol), apigenin, and stigmasterol (-8.3 kcal mol). Similarly, NS5 has shown favorable outcomes with apigenin (-9.9 kcal mol), rutin (-9.3 kcal mol), nigellicine (-9.1 kcal mol), and stigmasterol (-8.8 kcal mol). MD simulations validated the structural flexibility of the NS2B/NS3-taraxerol and NS5-apigenin docking complexes based on an RMSF value below 5 Å. The study concluded that among the understudied phytocomponents of , apigenin, nigellicine, nigellidine, dithymoquinone, taraxerol, campesterol, cycloeucalenol, stigmasterol and beta-sitosterol have been revealed as potential drug candidates, expected to show antiviral activity and promising drug likeliness. Phytochemicals on the short list may serve as inspiration for the creation of new drugs in the future. Further examination will assist in elucidating the molecular complexity of therapeutic and antiviral capabilities, opening several opportunities for researchers to identify novel medications throughout the drug development process.

摘要

登革热是一种传染性极强且传播迅速的媒介传播疾病,被世界卫生组织列为被忽视的热带病(NTD),因为它主要影响世界上的贫困人口,并且在历史上没有得到与其他疾病同等程度的关注。登革病毒NS2B/NS3蛋白酶和NS5聚合酶因其在病毒复制周期中的关键作用而被视为重要的潜在治疗靶点。迄今为止,尚无针对登革热的特异性抗病毒药物。常用的草药植物以其抗菌、抗病毒、抗炎、伤口愈合和皮肤病学特性而闻名。然而,关于其对登革病毒抗病毒作用的研究报道不足。当前的研究使用了几种预测技术来预测物质的口服生物利用度、类药性以及无毒和无致突变作用,这可能会促成新型、更安全药物的开发。因此,本研究旨在探索[草药名称]中的18种植物化学物质对登革病毒的两种重要酶NS2B/NS3和NS5的抑制潜力。对于NS2B/NS3,羽扇豆醇(-9.1千卡/摩尔)、异槲皮素(-8.4千卡/摩尔)、芹菜素和豆甾醇(-8.3千卡/摩尔)已观察到有前景的结果。同样,对于NS5,芹菜素(-9.9千卡/摩尔)、芦丁(-9.3千卡/摩尔)、黑种草碱(-9.1千卡/摩尔)和豆甾醇(-8.8千卡/摩尔)也显示出良好的结果。分子动力学模拟基于低于5埃的均方根波动(RMSF)值验证了NS2B/NS3 - 羽扇豆醇和NS5 - 芹菜素对接复合物的结构灵活性。该研究得出结论,在[草药名称]未充分研究的植物成分中,芹菜素、黑种草碱、黑种草啶、二氢胸腺醌、羽扇豆醇、菜油甾醇、环桉醇、豆甾醇和β - 谷甾醇已被揭示为潜在的药物候选物,有望显示抗病毒活性和良好的类药性。入围名单上的植物化学物质可能会为未来新药的研发提供灵感。进一步的研究将有助于阐明治疗和抗病毒能力的分子复杂性,为研究人员在整个药物开发过程中识别新型药物提供多个机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bf5/10273825/895385d57305/d3ra02613b-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bf5/10273825/479460b88b1b/d3ra02613b-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bf5/10273825/b55d95bb96b2/d3ra02613b-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bf5/10273825/59dec282d519/d3ra02613b-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bf5/10273825/475066b71383/d3ra02613b-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bf5/10273825/b59662312d90/d3ra02613b-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bf5/10273825/895385d57305/d3ra02613b-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bf5/10273825/479460b88b1b/d3ra02613b-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bf5/10273825/b55d95bb96b2/d3ra02613b-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bf5/10273825/59dec282d519/d3ra02613b-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bf5/10273825/475066b71383/d3ra02613b-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bf5/10273825/b59662312d90/d3ra02613b-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bf5/10273825/895385d57305/d3ra02613b-f6.jpg

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本文引用的文献

[1]
Ligand-based pharmacophore modeling and QSAR approach to identify potential dengue protease inhibitors.

Front Mol Biosci. 2023-2-23

[2]
Evaluation of the interaction between potent small molecules against the Nipah virus Glycoprotein in Malaysia and Bangladesh strains, accompanied by the human Ephrin-B2 and Ephrin-B3 receptors; a simulation approach.

Mol Divers. 2024-4

[3]
Engineering Modified mRNA-Based Vaccine against Dengue Virus Using Computational and Reverse Vaccinology Approaches.

Int J Mol Sci. 2022-11-11

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A Computational Approach Applied to the Study of Potential Allosteric Inhibitors Protease NS2B/NS3 from Dengue Virus.

Molecules. 2022-6-27

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Molecular Docking Approach of Bryophyllum Pinnatum Compounds as Atherosclerosis Therapy By Targeting Adenosine Monophosphate-Activated Protein Kinase and Inducible Nitric Oxide Synthase.

Acta Inform Med. 2022-6

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In Silico Analysis of the Apoptotic and HPV Inhibitory Roles of Some Selected Phytochemicals Detected from the Rhizomes of Greater Cardamom.

Appl Biochem Biotechnol. 2022-10

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Chemical Reactivity and Optical and Pharmacokinetics Studies of 14 Multikinase Inhibitors and Their Docking Interactions Toward ACK1 for Precision Oncology.

Front Chem. 2022-4-14

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Seawater fungi-derived compound screening to identify novel small molecules against dengue virus NS5 methyltransferase and NS2B/NS3 protease.

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Phytochemical Compound Screening to Identify Novel Small Molecules against Dengue Virus: A Docking and Dynamics Study.

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