Natural Products and Bioprospecting ( IF 4.8 ) Pub Date : 2020-10-22 , DOI: 10.1007/s13659-020-00275-9 Mohammed A Dahab 1 , Mostafa M Hegazy 2 , Hatem S Abbass 2, 3
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Abstract
Total 40 natural compounds were selected to perform the molecular docking studies to screen and identify the potent antiviral agents specifically for Severe Acute Respiratory Syndrome Coronavirus 2 that causes coronavirus disease 2019 (COVID-19). The key targets of COVID-19, protease (PDB ID: 7BQY) and RNA polymerase (PDB ID: 7bV2) were used to dock our target compounds by Molecular Operating Environment (MOE) version 2014.09. We used 3 different conformations of protease target (6M0K, 6Y2F and 7BQY) and two different score functions to strengthen the probability of inhibitors discovery. After an extensive screening analysis, 20 compounds exhibit good binding affinities to one or both COVID-19 targets. 7 out of 20 compounds were predicted to overcome the activity of both targets. The top 7 hits are, flacourticin (3), sagerinic acid (16), hordatine A (23), hordatine B (24), N-feruloyl tyramine dimer (25), bisavenanthramides B-5 (29) and vulnibactins (40). According to our results, all these top hits was found to have a better binding scores than remdesivir, the native ligand in RNA polymerase target (PDB ID: 7bV2). Hordatines are phenolic compounds present in barley, were found to exhibit the highest binding affinity to both protease and polymerase through forming strong hydrogen bonds with the catalytic residues, as well as significant interactions with other receptor-binding residues. These results probably provided an excellent lead candidate for the development of therapeutic drugs against COVID-19. Eventually, animal experiment and accurate clinical trials are needed to confirm the preventive potentials of these compounds.
Graphic Abstract
中文翻译：
大麦苷作为 COVID-19 主要蛋白酶和 RNA 聚合酶的潜在抑制剂：一种计算机模拟方法
摘要
总共选择了 40 种天然化合物进行分子对接研究，以筛选和鉴定专门针对引起 2019 年冠状病毒病（COVID-19）的严重急性呼吸系统综合症冠状病毒 2 的有效抗病毒药物。COVID-19、蛋白酶（PDB ID：7BQY）和RNA聚合酶（PDB ID：7bV2）的关键靶标用于通过分子操作环境（MOE）2014.09版本对接我们的靶标化合物。我们使用 3 种不同构象的蛋白酶靶标（6M0K、6Y2F 和 7BQY）和两种不同的评分函数来增强抑制剂发现的概率。经过广泛的筛选分析，20 种化合物对一个或两个 COVID-19 靶点表现出良好的结合亲和力。预计 20 种化合物中有 7 种能够克服这两个目标的活性。排名前 7 位的药物为：flacourticin (3)、sagerinic Acid (16)、hordatine A (23)、hordatine B (24)、N-阿魏酰酪胺二聚体(25)、bisavenanthramides B-5 (29)和 vulnibactins (40)。根据我们的结果，所有这些热门命中均比 RNA 聚合酶靶标中的天然配体瑞德西韦 (PDB ID：7bV2) 具有更好的结合分数。大麦苷是存在于大麦中的酚类化合物，通过与催化残基形成强氢键，以及与其他受体结合残基的显着相互作用，发现其对蛋白酶和聚合酶表现出最高的结合亲和力。这些结果可能为开发针对 COVID-19 的治疗药物提供了极好的先导候选药物。最终，需要动物实验和准确的临床试验来确认这些化合物的预防潜力。
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