Biophysics Department, Faculty of Sciences, Cairo University, Giza, Egypt.
Biophysics Section of Physics Department, Faculty of Sciences, Helwan University, Cairo, Egypt.
J Biomol Struct Dyn. 2021 May;39(8):2923-2931. doi: 10.1080/07391102.2020.1758789. Epub 2020 Apr 27.
The Middle East Respiratory Syndrome Coronavirus (MERS CoV), also termed camel flu, is a new viral infection that first reported in the year 2012 in the Middle East region and further spread during the last seven years. MERS CoV is characterized by its high mortality rate among different human coronaviruses. MERS CoV polymerase shares more than 20% sequence identity with the Hepatitis C Virus (HCV) Non-structural 5b (NS5b) RNA dependent RNA polymerase (RdRp). Despite the low sequence identity, the active site is conserved between the two proteins, with two consecutive aspartates that are crucial in the nucleotide transfer reaction. In this study, seven nucleotide inhibitors have been tested against MERS CoV RdRp using molecular modeling and docking simulations, from which four are novel compounds. Molecular Dynamics Simulation for 260 nanoseconds is performed on the MERS CoV RdRp model to test the effect of protein dynamics on the binding affinities to the tested nucleotide inhibitors. Results support the hypothesis of using the anti-polymerases (Anti-HCV drugs) against MERS CoV RdRp as a potent candidates. Besides four novel compounds are suggested as a seed for high performance inhibitors against MERS CoV RdRp.Communicated by Ramaswamy H. Sarma.
中东呼吸综合征冠状病毒（MERS-CoV），也称为骆驼流感，是一种新的病毒感染，于 2012 年首次在中东地区报告，并在过去七年中进一步传播。MERS-CoV 的特点是在不同的人类冠状病毒中具有较高的死亡率。MERS-CoV 聚合酶与丙型肝炎病毒（HCV）非结构 5b（NS5b）RNA 依赖性 RNA 聚合酶（RdRp）的序列相似度超过 20％。尽管序列相似度低，但两个蛋白质的活性位点是保守的，其中两个连续的天冬氨酸在核苷酸转移反应中至关重要。在这项研究中，使用分子建模和对接模拟测试了针对 MERS-CoV RdRp 的七种核苷酸抑制剂，其中四种是新型化合物。对 MERS-CoV RdRp 模型进行了 260 纳秒的分子动力学模拟，以测试蛋白质动力学对测试的核苷酸抑制剂结合亲和力的影响。结果支持使用抗聚合酶（抗 HCV 药物）来抑制 MERS-CoV RdRp 的假设，作为一种有效的候选药物。此外，还建议将四种新型化合物作为针对 MERS-CoV RdRp 的高效抑制剂的种子。Ramaswamy H. Sarma 通讯。
