通过计算将天然黄酮果胶素锁定为抗击 SARS-CoV-2 的有望候选药物

IF 2.7 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Current Research in Structural Biology Pub Date : 2023-12-15 DOI:10.1016/j.crstbi.2023.100120
Mukta Rani , Amit Kumar Sharma , R.S. Chouhan , Souvik Sur , Rani Mansuri , Rajesh K. Singh
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引用次数: 0

摘要

冠状病毒病-2019(COVID-19)已成为一种全球性流行病,因此有必要开发新的药物。在这项研究中,我们发现了潜在的天然黄酮类化合物,并比较了它们对穗状糖蛋白的抑制活性,穗状糖蛋白是 SARS-CoV-2 和 SARS-CoV 的靶点。用于治疗 SARS-CoV-2 的新抑制剂相互作用的目标位点具有 82% 的序列相同性,其余 18% 与 RBD S1-亚基、S2-亚基以及 2.5% 的其他位点存在差异。分子对接法分析了由 85 种天然类黄酮组成的配体库中每种配体的各种结合过程,这些配体可作为抗病毒药物和 FDA 批准的 COVID-19 治疗药物。根据对接分析,在目标活性位点的结合口袋中,雷米替韦的结合相互作用小于果胶素。Pectolinarin 是一种从 Cirsiumsetidensas 中分离出来的天然类黄酮,具有抗癌、舒张血管、抗炎、保肝、抗糖尿病、抗微生物和抗氧化等特性。S 糖蛋白 RBD 区(330-583)受到山奈酚、雷公藤苷和除草定的抑制,但 S2 亚基(686-1270)受到果胶苷、吗啉和雷米替韦的抑制。基于高对接分数,在 100ns 时对 SARS-CoV-2 的 S-糖蛋白与pectolinarin 复合物进行 MD 模拟分析。最后,利用 ADMET 分析验证了结合能最高的化合物。
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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Natural flavonoid pectolinarin computationally targeted as a promising drug candidate against SARS-CoV-2

Coronavirus disease-2019 (COVID-19) has become a global pandemic, necessitating the development of new medicines. In this investigation, we identified potential natural flavonoids and compared their inhibitory activity against spike glycoprotein, which is a target of SARS-CoV-2 and SARS-CoV. The target site for the interaction of new inhibitors for the treatment of SARS-CoV-2 has 82% sequence identity and the remaining 18% dissimilarities in RBD S1-subunit, S2-subunit, and 2.5% others. Molecular docking was employed to analyse the various binding processes used by each ligand in a library of 85 natural flavonoids that act as anti-viral medications and FDA authorised treatments for COVID-19. In the binding pocket of the target active site, remdesivir has less binding interaction than pectolinarin, according to the docking analysis. Pectolinarin is a natural flavonoid isolated from Cirsiumsetidensas that has anti-cancer, vasorelaxant, anti-inflammatory, hepatoprotective, anti-diabetic, anti-microbial, and anti-oxidant properties. The S-glycoprotein RBD region (330–583) is inhibited by kaempferol, rhoifolin, and herbacetin, but the S2 subunit (686–1270) is inhibited by pectolinarin, morin, and remdesivir. MD simulation analysis of S-glycoprotein of SARS-CoV-2 with pectolinarin complex at 100ns based on high dock-score. Finally, ADMET analysis was used to validate the proposed compounds with the highest binding energy.

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