研究药材中的大黄素衍生物对 SARS-CoV-2 的抗药性

IF 1.2 4区 综合性期刊 Q3 MULTIDISCIPLINARY SCIENCES
Talambedu Usha , Kadabagere Narayanaswamy Hemavathi , Arvind Kumar Goyal , C.S. Abhinand , S. Dhivya , A. Cholarajan , Neelu Joshi , Dinesh Babu , Sushil Kumar Middha
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引用次数: 0

摘要

SARS-CoV-2 继续以惊人的速度变异并在世界各地流行,新变种 JN.1 的出现就是一个例证。新型 SARS-CoV 变种的出现凸显了开发新药的紧迫性。植物化学物质以其安全性和有效性著称,已被广泛用于治疗各种疾病。本研究旨在确定大黄素(一种生物活性蒽醌)及其衍生物的抗 SARS-CoV 潜力。研究以 SARS-CoV 的血凝素-酯酶(HE)、木瓜蛋白酶样蛋白酶(PLpro)、主要蛋白酶(3CLpro)、非结构蛋白(nsp3)和尖峰蛋白(S)等关键蛋白为蛋白质靶标,虚拟筛选了 110 种大黄素衍生物(ED)和雷米替韦(一种成熟的抗病毒药物)。在 110 种衍生物中,ED21、ED25 和 ED5 分别抑制了 HE、3CLpro 和 S 蛋白。ED29 以较高的结合亲和力抑制 PLpro 和 nsp3。雷米替韦和大黄素衍生物占据了类似的受体结合位点。与雷米替韦相比,这些大黄素衍生物与受体中相似的氨基酸结合。对 ED21-HE、ED25-3CLpro、ED5-S、ED29-PLpro 和 ED29-nsp3 复合物的进一步动态模拟研究表明,所有这些复合物都很稳定,均方根偏差(RMSD)、均方根波动(RMSF)、可溶解表面积(SASA)和回旋半径(Rg)都很小,与 APO 蛋白质相当。所有配体都接受利宾斯基的五项法则。吸收、分布、代谢、排泄和毒性(ADMET)分析表明,只有 ED21 和 ED5 有希望成为具有高治疗价值且无副作用的类药物。这些分子内研究结果有助于开发强效的 SARS-CoV-2 抑制剂,从而有可能推动对有效抗病毒药物的探索。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Investigating emodin derivatives against SARS-CoV-2 found in medicinal herbs

Investigating emodin derivatives against SARS-CoV-2 found in medicinal herbs

SARS-CoV-2 continues to mutate and circulate at alarming levels around the world and is exemplified by the emergence of the new variant JN.1. The emergence of novel SARS-CoV variants underscores the urgency for the development of new drugs. Phytochemicals, known for their safety and efficacy, have been widely used to address various ailments. This study aims at identifying the anti-SARS-CoV potential of emodin, a bioactive anthraquinone, and its derivatives. Key proteins, including hemagglutinin-esterase (HE), papain-like protease (PLpro), major protease (3CLpro), non-structural protein (nsp3) and spike protein(S) of SARS-CoV, were used as protein targets for the virtual screening of 110 emodin derivatives (ED) and remdesivir a proven antiviral drug. Among the 110 derivatives, ED21, ED25, ED5 inhibited HE, 3CLpro and S protein, respectively. ED29 inhibited both PLpro and nsp3 with high binding affinity. Similar receptor binding sites were occupied by remdesivir and emodin derivatives. These emodin derivatives are bound to similar amino acids in receptors as compared to remdesivir. Further dynamic simulations studies with ED21-HE, ED25-3CLpro, ED5-S, ED29-PLpro and ED29-nsp3 complexes showed all of them are stable with minimum root mean square deviation (RMSD), root mean square fluctuation (RMSF), solvent-accessible surface area (SASA) and radius of gyration (Rg) and are comparable to APO protein. All the ligands accepted Lipinski's rule of five. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis revealed only ED21 and ED5 as promising druglike candidates that can have high therapeutic value and no side effects. These in-silico findings contribute to the development of potent SARS-CoV-2 inhibitors, potentially advancing the quest for effective antiviral drugs.

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来源期刊
Kuwait Journal of Science
Kuwait Journal of Science MULTIDISCIPLINARY SCIENCES-
CiteScore
1.60
自引率
28.60%
发文量
132
期刊介绍: Kuwait Journal of Science (KJS) is indexed and abstracted by major publishing houses such as Chemical Abstract, Science Citation Index, Current contents, Mathematics Abstract, Micribiological Abstracts etc. KJS publishes peer-review articles in various fields of Science including Mathematics, Computer Science, Physics, Statistics, Biology, Chemistry and Earth & Environmental Sciences. In addition, it also aims to bring the results of scientific research carried out under a variety of intellectual traditions and organizations to the attention of specialized scholarly readership. As such, the publisher expects the submission of original manuscripts which contain analysis and solutions about important theoretical, empirical and normative issues.
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