Chemical Engineering Department, Faculty of Engineering, Shahid Bahonar University of Kerman, Kerman, Iran.
Chemical Engineering Department, Faculty of Engineering, Vali-e-Asr, University of Rafsanjan, Rafsanjan, Iran.
Curr Microbiol. 2022 Jul 6;79(8):241. doi: 10.1007/s00284-022-02921-6.
D614G is one of the most reported mutations in the spike protein of SARS-COV-2 that has altered some crucial characteristics of coronaviruses, such as rate of infection and binding affinities. The binding affinity of different antiviral drugs was evaluated using rigid molecular docking. The reliability of the docking results was evaluated with the induced-fit docking method, and a better understanding of the drug-protein interactions was performed using molecular dynamics simulation. The results show that the D614G variant could change the binding affinity of antiviral drugs and spike protein remarkably. Although Cytarabine showed an appropriate interaction with the wild spike protein, Ribavirin and PMEG diphosphate exhibited a significant binding affinity to the mutated spike protein. The parameters of the ADME/T analysis showed that these drugs are suitable for further in-vitro and in-vivo investigation. D614G alteration affected the binding affinity of the RBD and its receptor on the cell surface.
D614G 是 SARS-CoV-2 刺突蛋白中报告最多的突变之一,它改变了冠状病毒的一些关键特征,如感染率和结合亲和力。使用刚性分子对接评估了不同抗病毒药物的结合亲和力。通过诱导契合对接方法评估对接结果的可靠性,并通过分子动力学模拟更好地了解药物-蛋白质相互作用。结果表明,D614G 变体可以显著改变抗病毒药物和刺突蛋白的结合亲和力。虽然阿糖胞苷与野生刺突蛋白表现出适当的相互作用,但利巴韦林和 PMEG 二磷酸对突变刺突蛋白表现出显著的结合亲和力。ADME/T 分析的参数表明,这些药物适合进一步的体外和体内研究。D614G 改变影响了 RBD 及其在细胞表面上的受体的结合亲和力。