Molecular Diversity ( IF 3.9 ) Pub Date : 2021-01-03 , DOI: 10.1007/s11030-020-10178-z Abdo A Elfiky 1 , Eman B Azzam 2 , Medhat W Shafaa 2
|
Abstract
Coronavirus diseases 2019 (COVID-19) are seriously affecting human health all over the world. Nucleotide inhibitors have promising results in terms of its efficacy against different viral polymerases. In this study, detailed molecular docking and dynamics simulations are used to evaluate the binding affinity of a clinically approved drug, sofosbuvir, with the solved structure of the viral protein RNA-dependent RNA polymerase (RdRp) and compare it to the clinically approved drug, Remdesivir. These drugs are docked onto the three-dimensional structure of the nsp12 protein of SARS-CoV-2, which controls the polymerization process. Hence, it is considered one of the primary therapeutic targets for coronaviruses. Sofosbuvir is a drug that is currently used for HCV treatment; therefore, HCV RdRp is used as a positive control protein target. The protein dynamics are simulated for 100 ns, while the binding is tested during different dynamics states of the SARS-CoV-2 RdRp. Additionally, the drug-protein complexes are further simulated for 20 ns to explore the binding mechanism. The interaction of SARS-CoV-2 RdRp as a target with the active form of sofosbuvir as a ligand demonstrates binding effectiveness. One of the FDA-approved antiviral drugs, such as sofosbuvir, can help us in this mission, aiming to limit the danger of COVID-19. Sofosbuvir was found to bind nsp12 with comparable binding energies to that of Remdesivir, which has been reported for its potential against COVID-19 RdRp and is currently approved by the FDA.
Graphic abstract
中文翻译：
抗 HCV 药物索磷布韦 (Sofosbuvir) 与抗 EBOV 药物瑞德西韦 (Remdesivir) 的计算机模拟对抗 SARS-CoV-2 RNA 依赖性 RNA 聚合酶
抽象的
2019 年冠状病毒病（COVID-19）严重影响全世界人类健康。核苷酸抑制剂在对抗不同病毒聚合酶的功效方面具有令人鼓舞的结果。在这项研究中，使用详细的分子对接和动力学模拟来评估临床批准的药物索磷布韦与病毒蛋白RNA依赖性RNA聚合酶（RdRp）的已解析结构的结合亲和力，并将其与临床批准的药物进行比较，瑞德西韦。这些药物对接在 SARS-CoV-2 的 nsp12 蛋白的三维结构上，控制聚合过程。因此，它被认为是冠状病毒的主要治疗靶点之一。 Sofosbuvir是目前用于HCV治疗的药物；因此，HCV RdRp 被用作阳性对照蛋白靶标。蛋白质动力学模拟 100 ns，同时在 SARS-CoV-2 RdRp 的不同动力学状态下测试结合。此外，进一步模拟药物-蛋白质复合物 20 ns，以探索结合机制。 SARS-CoV-2 RdRp 作为靶标与索非布韦活性形式作为配体的相互作用证明了结合有效性。 FDA 批准的一种抗病毒药物，例如索磷布韦，可以帮助我们完成这一使命，旨在限制 COVID-19 的危险。索磷布韦被发现以与瑞德西韦相当的结合能与 nsp12 结合，据报道瑞德西韦具有对抗 COVID-19 RdRp 的潜力，目前已获得 FDA 批准。
京公网安备 11010802027423号