Adenosyl derivatives as a potential inhibitors of NS3 protease of Japanese encephalitis virus (JEV): In silico molecular insight into therapeutic discovery

IF 3 3区化学 Q3 CHEMISTRY, PHYSICAL

Computational and Theoretical Chemistry Pub Date : 2024-09-19 DOI:10.1016/j.comptc.2024.114848

Rakesh Kumar Tiwari, Vinayak Pandey, R.P. Ojha, Vishnudatt Pandey, Muralidhar Pandey

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Abstract

The genus Flavivirus NS3 a non-structural protein of Japanes Encephalitis Virus (JEV), a serious deadly human pathogen responsible for several deaths in South East Asia, consists of helicase/NTPase domain forming a cleft known for their role in the enzymatic activity and viral replication represented biological relevance. S-Adenosyl derivatives act as powerful inhibitors in viral replication in NS5 of the same genus as of NS3, provide a powerful base to test its effectiveness in NS3 protein due to the compatibility of both proteins. The MM-GBSA (Molecular Mechanics-Generalized Born Surface Area) simulation were performed to evaluate the binding free energy, following the 100 (ns) production MD simulation in the periodic boundary condition (PBC) for the selected docked inhibitors with NS3. The residue-wise decomposition energy determined in our study revealed the active site region made the high stability with the potential inhibitors.

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腺苷衍生物作为日本脑炎病毒（JEV）NS3蛋白酶的潜在抑制剂：从硅学分子角度洞察治疗发现

日本脑炎病毒（JEV）是一种严重的致命性人类病原体，在东南亚地区造成了数起死亡病例，它的非结构性蛋白质由螺旋酶/NTPase结构域组成，形成一个裂隙，在酶活性和病毒复制中的作用具有生物学意义。S-Adenosyl 衍生物在同属 NS3 的 NS5 病毒复制中起着强大的抑制作用，由于这两种蛋白的兼容性，为测试其在 NS3 蛋白中的有效性提供了有力的依据。在周期性边界条件（PBC）下对所选抑制剂与 NS3 的对接进行 100 (ns) 次生产 MD 模拟后，进行了 MM-GBSA（分子力学-广义玻恩表面积）模拟，以评估其结合自由能。我们的研究确定的残基分解能揭示了潜在抑制剂具有高稳定性的活性位点区域。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Computational and Theoretical Chemistry CHEMISTRY, PHYSICAL-

CiteScore

4.20

自引率

10.70%

发文量

331

审稿时长

31 days

期刊介绍： Computational and Theoretical Chemistry publishes high quality, original reports of significance in computational and theoretical chemistry including those that deal with problems of structure, properties, energetics, weak interactions, reaction mechanisms, catalysis, and reaction rates involving atoms, molecules, clusters, surfaces, and bulk matter.