Department of Biology, College of Science, University of Hail, P.O. Box 2440, Ha'il 2440, Saudi Arabia.
Laboratory of Genetics, Biodiversity and Valorisation of Bioressources, High Institute of Biotechnology, University of Monastir, Monastir 5000, Tunisia.
Molecules. 2022 Apr 8;27(8):2401. doi: 10.3390/molecules27082401.
SARS-CoV-2 is a highly virulent coronavirus that first surfaced in late 2019 and has since created a pandemic of the acute respiratory sickness known as "coronavirus disease 2019" (COVID-19), posing a threat to human health and public safety. S-RBD is a coronaviral protein that is essential for a coronavirus (CoV) to bind and penetrate into host cells. As a result, it has become a popular pharmacological target. The goal of this study was to find potential candidates for anti-coronavirus disease 2019 (COVID-19) drugs by targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S-RBD with novel bioactive compounds and molecular interaction studies of 15,000 phytochemicals belonging to different flavonoid subgroups. A spike protein crystal structure attached to the ACE2 structure was obtained from the PDB database. A library of 15,000 phytochemicals was made by collecting compounds from different databases, such as the Zinc-database, PubChem-database, and MPD3-database. This library was docked against a receptor binding domain of a spike glycoprotein through the Molecular Operating Environment (MOE). The top drug candidates Phylloflavan, Milk thistle, Ilexin B and Isosilybin B, after virtual screening, were selected on the basis of the least binding score. Phylloflavan ranked as the top compound because of its least binding affinity score of -14.09 kcal/mol. In silico studies showed that all those compounds showed good activity and could be used as an immunological response with no bioavailability issues. Absorption, distribution, metabolism, excretion and a toxicological analysis were conducted through SwissADME. Stability and effectiveness of the docked complexes were elucidated by performing the 100 ns molecular dynamic simulation through the Desmond package.
SARS-CoV-2 是一种高毒力的冠状病毒，于 2019 年末首次出现，并由此引发了一种名为“2019 年冠状病毒病”（COVID-19）的急性呼吸道疾病大流行，对人类健康和公共安全构成威胁。S-RBD 是冠状病毒（CoV）结合并穿透宿主细胞所必需的冠状病毒蛋白。因此，它已成为一个热门的药理学靶点。本研究的目的是通过针对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）S-RBD 与新型生物活性化合物，以及对属于不同黄酮类亚组的 15000 种植物化学物质的分子相互作用研究，寻找抗 2019 年冠状病毒病（COVID-19）药物的潜在候选药物。从 PDB 数据库中获得了附着在 ACE2 结构上的刺突蛋白晶体结构。通过从不同数据库（如 Zinc-database、PubChem-database 和 MPD3-database）收集化合物，构建了一个包含 15000 种植物化学物质的文库。通过分子操作环境（MOE）将该文库对接至刺突糖蛋白的受体结合域。经过虚拟筛选，根据最低结合评分，选择 Phylloflavan、奶蓟草、Ilexin B 和 Isosilybin B 作为前 3 名候选药物。由于其最低结合亲和力评分为-14.09 kcal/mol，Phylloflavan 排名第一。计算机研究表明，所有这些化合物都表现出良好的活性，可以作为一种免疫反应，且不存在生物利用度问题。通过 SwissADME 进行吸收、分布、代谢、排泄和毒理学分析。通过使用 Desmond 包进行 100 ns 分子动力学模拟，阐明了对接复合物的稳定性和有效性。
