Background: Coronavirus disease 2019 (COVID-19) has caused a global pandemic with a high mortality rate and infecting people worldwide. The COVID-19 vaccines that are currently in development or already approved are expected to provide at least some protection against the emerging variants of the virus but the mutations may reduce the efficacy of the existing vaccines. Purified phytochemicals from medicinal plants provide a helpful framework for discovering new therapeutic leads as they have long been employed in traditional medicine to treat many disorders. Objective: The objectives of the study are to exploit the anti-HIV bioactive compounds against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) through molecular docking studies and perform the Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties of potential compounds. Methods: Molecular docking was performed to study the interaction of ligands with the target sites of RdRp protein (PDB: 6M71) using AutoDock Vina. The ADMET properties of potential compounds were predicted using the pkCSM platform. Results: A total of 151 phytochemicals derived from the medicinal plants with recognized antiviral activity and 18 anti-HIV drugs were virtually screened against COVID-19 viral RdRp to identify putative inhibitors that facilitate the development of potential anti-COVID-19 drug candidates. The computational studies identified 34 compounds and three drugs inhibiting viral RdRp with binding energies ranging from -10.2 to -8.5 kcal/ mol. Among these, five compounds, namely Michellamine B, Quercetin 3-O-(2'',6''-digalloyl)-beta-D-galactopyranoside, Corilagin, Hypericin, and 1,2,3,4,6-Penta-O-galloyl-beta-D-glucose residues bound efficiently with the binding site of RdRp. Besides, Lopinavir, Maraviroc, and Remdesivir drugs also inhibited SARS-CoV-2 polymerase. In addition, the ADMET properties of top potential compounds were also predicted in comparison to the drugs. Conclusion: The present study suggested that these potential drug candidates can be further subjected to in vitro and in vivo studies that may help develop effective anti-COVID-19 drugs.

中文翻译：

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重新定位 SARS-CoV-2 的治疗方法：虚拟筛选基于植物的抗 HIV 化合物作为 COVID-19 病毒 RdRp 的可能抑制剂

背景：2019 年冠状病毒病（COVID-19）已引起全球大流行，死亡率很高，并感染了全世界的人。目前正在开发或已经批准的 COVID-19 疫苗有望至少提供一些针对新出现的病毒变体的保护，但突变可能会降低现有疫苗的功效。从药用植物中提纯的植物化学物质为发现新的治疗线索提供了一个有用的框架，因为它们长期以来一直在传统医学中用于治疗许多疾病。目的：本研究的目的是通过分子对接研究开发抗 SARS-CoV-2 RNA 依赖性 RNA 聚合酶 (RdRp) 的抗 HIV 生物活性化合物，并进行吸收、分布、代谢、排泄和毒性 (ADMET) 特性的潜在化合物。方法：使用 AutoDock Vina 进行分子对接，研究配体与 RdRp 蛋白（PDB：6M71）靶位点的相互作用。使用 pkCSM 平台预测了潜在化合物的 ADMET 特性。结果：针对 COVID-19 病毒 RdRp 虚拟筛选了总共 151 种源自具有公认抗病毒活性的药用植物的植物化学物质和 18 种抗 HIV 药物，以确定可促进潜在抗 COVID-19 候选药物开发的推定抑制剂。计算研究确定了 34 种化合物和三种抑制病毒 RdRp 的药物，结合能范围为 -10.2 至 -8.5 kcal/mol。其中，五种化合物，即 Michellamine B、槲皮素 3-O-(2'',6''-digalloyl)-β-D-galactopyranoside、Corilagin、Hypericin 和 1,2,3,4，6-Penta-O-没食子酰-β-D-葡萄糖残基与 RdRp 的结合位点有效结合。此外，洛匹那韦、马拉韦罗克和瑞德西韦药物也能抑制 SARS-CoV-2 聚合酶。此外，与药物相比，还预测了最有潜力的化合物的 ADMET 特性。结论：本研究表明，这些潜在的候选药物可以进一步进行体外和体内研究，这可能有助于开发有效的抗 COVID-19 药物。