The repurposing of FDA approved drugs is presently receiving attention for COVID-19 drug discovery. Previous studies revealed the binding potential of several FDA-approved drugs towards specific targets of SARS-CoV-2; however, limited studies are focused on the structural and molecular basis of interaction of these drugs towards multiple targets of SARS-CoV-2. The present study aimed to predict the binding potential of six FDA drugs towards fifteen protein targets of SARS-CoV-2 and propose the structural and molecular basis of the interaction by molecular docking and dynamic simulation. Based on the literature survey, fifteen potential targets of SARS-CoV-2, and six FDA drugs (Chloroquine, Hydroxychloroquine, Favipiravir, Lopinavir, Remdesivir, and Ritonavir) were selected. The binding potential of individual drug towards the selected targets was predicted by molecular docking in comparison with the binding of the same drugs with their usual targets. The stabilities of the best-docked conformations were confirmed by molecular dynamic simulation and energy calculations. Among the selected drugs, Ritonavir and Lopinavir showed better binding towards the prioritized targets with minimum binding energy (kcal/mol), cluster-RMS, number of interacting residues, and stabilizing forces when compared with the binding of Chloroquine, Favipiravir, and Hydroxychloroquine, later drugs demonstrated better binding when compared to the binding with their usual targets. Remdesvir showed better binding to the prioritized targets in comparison with the binding of Chloroquine, Favipiravir, and Hydroxychloroquine, but showed lesser binding potential when compared to the interaction between Ritonavir and Lopinavir and the prioritized targets. The structural and molecular basis of interactions suggest that the FDA drugs can be repurposed towards multiple targets of SARS-CoV-2, and the present computational models provide insights on the scope of repurposed drugs against COVID-19.

FDA 批准药物的重新利用目前在 COVID-19 药物发现中受到关注。先前的研究揭示了 FDA 批准的几种药物对 SARS-CoV-2 特定靶点的结合潜力；然而，有限的研究集中在这些药物与 SARS-CoV-2 多个靶点相互作用的结构和分子基础上。本研究旨在预测 6 种 FDA 药物与 SARS-CoV-2 15 个蛋白质靶标的结合潜力，并通过分子对接和动态模拟提出相互作用的结构和分子基础。根据文献调查，选择了 15 个 SARS-CoV-2 的潜在靶点和 6 种 FDA 药物（氯喹、羟氯喹、法匹拉韦、洛匹那韦、瑞德西韦和利托那韦）。通过分子对接，与相同药物与其通常靶标的结合进行比较，预测单个药物对选定靶标的结合潜力。通过分子动力学模拟和能量计算证实了最佳对接构象的稳定性。在所选药物中，与氯喹、法维匹拉韦和羟氯喹的结合相比，利托那韦和洛匹那韦以最小结合能（kcal/mol）、簇-RMS、相互作用残基数量和稳定力对优先靶标表现出更好的结合，与通常的靶点相比，后来的药物表现出更好的结合。与氯喹、法维匹拉韦和羟氯喹的结合相比，瑞德西韦与优先靶标的结合更好，但与利托那韦和洛匹那韦与优先靶标之间的相互作用相比，其结合潜力较小。 相互作用的结构和分子基础表明，FDA 药物可以重新用于 SARS-CoV-2 的多个靶点，并且目前的计算模型提供了有关针对 COVID-19 的重新用途药物范围的见解。