Therapeutic switching of metronidazole anti-cancerous compounds as anti SARS-COV-2 inhibitors: integration of QSAR, molecular docking, MD simulation and ADMET analysis

IF 1.9 4区物理与天体物理 Q2 BIOLOGY

Origins of Life and Evolution of Biospheres Pub Date : 2024-08-09 DOI:10.1007/s11084-024-09653-6

Shagufta Parveen, Rabia Khalil, Nusrat Shafiq, Maryam Rashid, Zill-i-Huma Nazli, Turki M. Dawoud, Amira Metouekel, Mohammed Bourhia, Youssouf Ali younous, Aniqa Moveed

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Abstract

The global economy and public health are seriously at risk because of the COVID-19 outbreak brought on by the SARS-CoV-2. Currently, there is no specific medication available to treat COVID-19 patients. A quick method used to find out the treatment of newly developing infectious diseases like SARS COV-2 by drug repurposing. Metronidazole (3-methyl-5-nitroimidazole) is a synthetic, azomycin derivative having strong bacteriocidal and antiparasitic properties. Metronidazole (MTZ) derivatives are commercially broad spectrum containing pertinent antibacterial activity and a reasonable safety profile. MTZ structures were designed using chemdraw professional and subjected to field base and atom base QSAR and displayed good results by identifying 9 compounds as active. Molecular docking was performed with 9 proteins from which highest docking score was ranged from − 6.305 to − 8.044 of MT35 with 7aot as compared to standard drug (Lopinavir, showed docking score − 5.504 with same protein). Docking was further validated by redocking by RMSD score in range of 2 Å. MMGB/SA results showed the negative binding energy values of docked protein–ligand complexes comparable to standard drug and MD stimulation were also performed for the structure flexibility showed 1.00 Å RMSF for three protein at maximum fluctuation. Selected drug (MT35) showed good ADME properties which may need to be synthesized followed by in vitro and in vivo study against SARS-CoV-2.

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甲硝唑抗癌化合物作为抗 SARS-COV-2 抑制剂的治疗转换：QSAR、分子对接、MD 模拟和 ADMET 分析的整合

由于 SARS-CoV-2 导致 COVID-19 的爆发，全球经济和公众健康受到严重威胁。目前，还没有治疗 COVID-19 患者的特效药物。通过药物再利用，可以快速找到治疗像 SARS COV-2 这样的新发传染病的方法。甲硝唑（3-甲基-5-硝基咪唑）是一种人工合成的偶氮霉素衍生物，具有很强的杀菌和抗寄生虫特性。甲硝唑（MTZ）衍生物在商业上具有广谱性，含有相关的抗菌活性和合理的安全性。我们使用 chemdraw professional 软件设计了 MTZ 结构，并对其进行了场基和原子基 QSAR 分析。与 9 种蛋白质进行了分子对接，其中 MT35 与 7aot 的对接得分最高，从 - 6.305 到 - 8.044 不等，与标准药物（洛匹那韦，与相同蛋白质的对接得分为 - 5.504）进行了比较。MMGB/SA 结果显示，对接的蛋白质配体复合物的负结合能值与标准药物相当。所选药物（MT35）显示出良好的 ADME 特性，可能需要在合成后对 SARS-CoV-2 进行体外和体内研究。

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来源期刊

Origins of Life and Evolution of Biospheres 生物-生物学

CiteScore

3.20

自引率

15.00%

发文量

审稿时长

>12 weeks

期刊介绍： The subject of the origin and early evolution of life is an inseparable part of the general discipline of Astrobiology. The journal Origins of Life and Evolution of Biospheres places special importance on the interconnection as well as the interdisciplinary nature of these fields, as is reflected in its subject coverage. While any scientific study which contributes to our understanding of the origins, evolution and distribution of life in the Universe is suitable for inclusion in the journal, some examples of important areas of interest are: prebiotic chemistry and the nature of Earth''s early environment, self-replicating and self-organizing systems, the theory of the RNA world and of other possible precursor systems, and the problem of the origin of the genetic code. Early evolution of life - as revealed by such techniques as the elucidation of biochemical pathways, molecular phylogeny, the study of Precambrian sediments and fossils and of major innovations in microbial evolution - forms a second focus. As a larger and more general context for these areas, Astrobiology refers to the origin and evolution of life in a cosmic setting, and includes interstellar chemistry, planetary atmospheres and habitable zones, the organic chemistry of comets, meteorites, asteroids and other small bodies, biological adaptation to extreme environments, life detection and related areas. Experimental papers, theoretical articles and authorative literature reviews are all appropriate forms for submission to the journal. In the coming years, Astrobiology will play an even greater role in defining the journal''s coverage and keeping Origins of Life and Evolution of Biospheres well-placed in this growing interdisciplinary field.