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 SARS-CoV-2 引起的 2019 年冠状病毒病 (COVID-19) 的爆发已被认为是全球健康问题。由于尚无特定抗病毒药物被证明可有效治疗 COVID-19，因此迫切需要确定新的治疗方法。在这项研究中，使用计算方法分析了类黄酮化合物对 SARS-CoV-2 重要蛋白质靶点的抑制潜力。使用 COVID-19 对接服务器对从 PubChem 检索到的类黄酮化合物进行虚拟对接，以筛选 SARS-CoV-2 的主要蛋白酶。停靠分数的截止值设置为>−9 kcal/mol，并使用 AutoDock 4.1 软件将筛选的化合物分别与主要蛋白酶、RNA 依赖性 RNA 聚合酶和刺突蛋白进行对接。最后，对铅类黄酮化合物进行 ADMET 分析。针对主要蛋白酶靶标虚拟筛选了总共 458 种黄酮类化合物，并根据相互作用能值 >−9 kcal/mol 选择了 36 种化合物。此外，这些化合物分别与蛋白质靶点对接，并鉴定出前 10 种先导化合物。在先导化合物中，agathisflavone 对主要蛋白酶的结合能最高，为 -8.4 kcal/mol，Albireodlphin 对 RdRp 和 spike 蛋白的结合能最高，分别为 -9.8 kcal/mol 和 -11.2 kcal/mol。根据高码头分数和 ADMET 特性，排名前 5 的领先分子如 Albireodlphin、Apigenin 7-(6"-malonylglucoside)、Cyanidin-3-(p-coumaroyl)-rutinoside-5-glucoside、Delphinidin 3-O-beta -D-葡萄糖苷 5-O-(6-香豆酰基-β-D-葡萄糖苷) 和 (-)-Maackiain-3-O-葡萄糖基-6"-O-丙二酸酯被鉴定为主要蛋白酶、RdRp 和SARS-CoV-2 的刺突蛋白靶标。这些所有化合物均具有非致癌性和非致突变性。这项研究结果表明，筛选的化合物包括 Albireodlphin、Apigenin 7-(6″-malonylglucoside)、Cyanidin-3-(p-coumaroyl)-rutinoside-5-glucoside、Delphinidin 3-O-beta-D-glucoside 5-O -(6-香豆酰基-β-D-葡萄糖苷) 和 (-)-Maackiain-3-O-葡萄糖基-6"-O-丙二酸可能是 SARS-CoV-2 靶标的有效抑制剂。