Rameshkumar Marimuthu Ragavan, Indu Purushothaman, Arunagirinathan Narasingam, Venkatadri Babu, El-Serehy Hamed A, Ahmad Ajaz
Laboratory Division, ICMR-National Institute of Epidemiology, Chennai, India.
Department of Microbiology and Biotechnology, Presidency College (Autonomous), Affiliated to University of Madras, Chennai, India.
Saudi J Biol Sci. 2021 Jan;28(1):448-458. doi: 10.1016/j.sjbs.2020.10.028. Epub 2020 Oct 22.
An outbreak of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has been recognized as a global health concern. Since, no specific antiviral drug is proven effective for treatment against COVID-19, identification of new therapeutics is an urgent need. In this study, flavonoid compounds were analyzed for its inhibitory potential against important protein targets of SARS-CoV-2 using computational approaches. Virtual docking was performed for screening of flavonoid compounds retrieved from PubChem against the main protease of SARS-CoV-2 using COVID-19 docking server. The cut off of dock score was set to >-9 kcal/mol and screened compounds were individually docked against main protease, RNA-dependent RNA polymerase, and spike proteins using AutoDock 4.1 software. Finally, lead flavonoid compounds were subjected to ADMET analysis. A total of 458 flavonoid compounds were virtually screened against main protease target and 36 compounds were selected based on the interaction energy value >-9 kcal/mol. Furthermore, these compounds were individually docked against protein targets and top 10 lead compounds were identified. Among the lead compounds, agathisflavone showed highest binding energy value of -8.4 kcal/mol against main protease, Albireodelphin showed highest dock score of -9.8 kcal/mol and -11.2 kcal/mol against RdRp, and spike proteins, respectively. Based on the high dock score and ADMET properties, top 5 lead molecules such as Albireodelphin, Apigenin 7-(6″-malonylglucoside), Cyanidin-3-(p-coumaroyl)-rutinoside-5-glucoside, Delphinidin 3-O-beta-D-glucoside 5-O-(6-coumaroyl-beta-D-glucoside) and (-)-Maackiain-3-O-glucosyl-6″-O-malonate were identified as potent inhibitors against main protease, RdRp, and spike protein targets of SARS-CoV-2. These all compounds are having non-carcinogenic and non-mutagenic properties. This study finding suggests that the screened compounds include Albireodelphin, Apigenin 7-(6″-malonylglucoside), Cyanidin-3-(p-coumaroyl)-rutinoside-5-glucoside, Delphinidin 3-O-beta-D-glucoside 5-O-(6-coumaroyl-beta-D-glucoside) and (-)-Maackiain-3-O-glucosyl-6″-O-malonate could be the potent inhibitors of SARS-CoV-2 targets.
由严重急性呼吸综合征冠状病毒 2 型（SARS-CoV-2）引起的 2019 冠状病毒病（COVID-19）疫情已被视为全球卫生问题。由于尚无经证实对 COVID-19 有效的特定抗病毒药物，因此迫切需要鉴定新的治疗方法。在本研究中，使用计算方法分析了黄酮类化合物对 SARS-CoV-2 重要蛋白质靶点的抑制潜力。利用 COVID-19 对接服务器，对从 PubChem 检索到的黄酮类化合物与 SARS-CoV-2 的主要蛋白酶进行虚拟对接筛选。对接分数的截断值设定为 > -9 kcal/mol，筛选出的化合物使用 AutoDock 4.1 软件分别与主要蛋白酶、RNA 依赖性 RNA 聚合酶和刺突蛋白进行对接。最后，对先导黄酮类化合物进行了药物代谢及毒性预测（ADMET）分析。共对 458 种黄酮类化合物针对主要蛋白酶靶点进行了虚拟筛选，并根据相互作用能值 > -9 kcal/mol 选择了 36 种化合物。此外，将这些化合物分别与蛋白质靶点对接，鉴定出前 10 种先导化合物。在先导化合物中，阿盖黄酮对主要蛋白酶的结合能值最高，为 -8.4 kcal/mol，白滨红山茶素分别对 RNA 依赖性 RNA 聚合酶和刺突蛋白的对接分数最高，为 -9.8 kcal/mol 和 -11.2 kcal/mol。基于高对接分数和 ADMET 性质，确定了前 5 种先导分子，如白滨红山茶素、芹菜素 7-(6″-丙二酰葡萄糖苷)、矢车菊素-3-(对香豆酰)-芸香糖苷-5-葡萄糖苷、飞燕草素 3-O-β-D-葡萄糖苷 5-O-(6-香豆酰-β-D-葡萄糖苷)和(-)-马鞍树苷-3-O-葡萄糖基-6″-O-丙二酸酯，它们是针对 SARS-CoV-2 主要蛋白酶、RNA 依赖性 RNA 聚合酶和刺突蛋白靶点的有效抑制剂。所有这些化合物都具有非致癌和非致突变特性。本研究结果表明，筛选出的化合物，包括白滨红山茶素、芹菜素 7-(丙二酰葡萄糖苷)、矢车菊素-3-(对香豆酰)-芸香糖苷-5-葡萄糖苷、飞燕草素 3-O-β-D-葡萄糖苷 5-O-(6-香豆酰-β-D-葡萄糖苷)和(-)-马鞍树苷-3-O-葡萄糖基-6″-O-丙二酸酯，可能是 SARS-CoV-2 靶点的有效抑制剂。
