Department of Chemistry, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.
Micro-Analysis and Environmental Research and Community Services Center, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.
J Environ Sci Health A Tox Hazard Subst Environ Eng. 2020;55(11):1373-1386. doi: 10.1080/10934529.2020.1826192. Epub 2020 Oct 1.
This work aimed at evaluating the inhibitory effect of ten natural bioactive compounds (1-10) as potential inhibitors of SARS-CoV-2-3CL main protease (PDB ID: 6LU7) and SARS-CoV main proteases (PDB IDs: 2GTB and 3TNT) by molecular docking analysis. The inhibitory effect of all studied compounds was studied with compared to some proposed antiviral drugs which currently used in COVID-19 treatment such as chloroquine, hydroxychloroquine, azithromycin, remdesivir, baloxvir, lopinavir, and favipiravir. Homology modeling and sequence alignment was computed to evaluate the similarity between the SARS-CoV-2-3CL main protease and other SARS-CoV receptors. ADMET properties of all studied compounds were computed and reported. Also, molecular dynamic (MD) simulation was performed on the compound which has the highest binding affinity inside 6LU7 obtained from molecular docking analysis to study it is stability inside receptor in explicit water solvent. Based on molecular docking analysis, we found that caulerpin has the highest binding affinity inside all studied receptors compared to other bioactive compounds and studied drugs. Our homology modeling and sequence alignment showed that SARS-CoV main protease (PDB ID: 3TNT) shares high similarity with 3CLpro (96.00%). Also, ADMET properties confirmed that caulerpin obeys Lipinski's rule and passes ADMET property, which make it a promising compound to act as a new safe natural drug against SARS-CoV-2-3CL main protease. Finally, MD simulation confirmed that the complex formed between caulerpin and 3CLpro is stable in water explicit and had no major effect on the flexibility of the protein throughout the simulations and provided a suitable basis for our study. Also, binding free energy between caulerpin and 6LU7 confirmed the efficacy of the caulerpin molecule against SARS-CoV-2 main protease. So, this study suggested that caulerpin could be used as a potential candidate in COVID-19 treatment.
这项工作旨在通过分子对接分析评估十种天然生物活性化合物（1-10）作为 SARS-CoV-2-3CL 主要蛋白酶（PDB ID：6LU7）和 SARS-CoV 主要蛋白酶（PDB IDs：2GTB 和 3TNT）潜在抑制剂的抑制作用。与目前用于 COVID-19 治疗的一些抗病毒药物（如氯喹、羟氯喹、阿奇霉素、瑞德西韦、巴洛昔韦、洛匹那韦和法匹拉韦）相比，研究了所有研究化合物的抑制作用。同源建模和序列比对计算用于评估 SARS-CoV-2-3CL 主要蛋白酶与其他 SARS-CoV 受体之间的相似性。计算并报告了所有研究化合物的 ADMET 特性。此外，还对分子对接分析中获得的与 6LU7 结合亲和力最高的化合物进行了分子动力学（MD）模拟，以研究其在受体中在明水环境中的稳定性。基于分子对接分析，我们发现与其他生物活性化合物和研究药物相比，海角藻素在所有研究受体中具有最高的结合亲和力。我们的同源建模和序列比对表明，SARS-CoV 主要蛋白酶（PDB ID：3TNT）与 3CLpro （96.00%）具有高度相似性。此外，ADMET 特性证实海角藻素符合 Lipinski 规则并通过 ADMET 特性，这使其成为一种有前途的新型天然药物，可作为 SARS-CoV-2-3CL 主要蛋白酶的新安全药物。最后，MD 模拟证实海角藻素与 3CLpro 形成的复合物在明水环境中稳定，在整个模拟过程中对蛋白质的灵活性没有重大影响，并为我们的研究提供了合适的基础。此外，海角藻素与 6LU7 之间的结合自由能证实了海角藻素分子对 SARS-CoV-2 主要蛋白酶的功效。因此，这项研究表明海角藻素可用于 COVID-19 的治疗。
