PDF(Pubmed)
Abstract：
A non-structural SARS-CoV-2 protein, PLpro, is involved in post-translational modifications in cells, allowing the evasion of antiviral immune response mechanisms. In this study, potential PLpro inhibitory drugs were designed using QSAR, molecular docking, and molecular dynamics. A combined QSAR equation with physicochemical and Free-Wilson descriptors was formulated. The r2, q2, and r2test values were 0.833, 0.770, and 0.721, respectively. From the equation, it was found that the presence of an aromatic ring and a basic nitrogen atom is crucial for obtaining good antiviral activity. Then, a series of structures for the binding sites of C111, Y268, and H73 of PLpro were created. The best compounds were found to exhibit pIC50 values of 9.124 and docking scoring values of -14 kcal/mol. The stability of the compounds in the cavities was confirmed by molecular dynamics studies. A high number of stable contacts and good interactions over time were exhibited by the aryl-thiophenes Pred14 and Pred15, making them potential antiviral candidates.
摘要：
一种非结构性SARS-CoV-2蛋白,PLpro,参与细胞中的翻译后修饰，允许逃避抗病毒免疫应答机制。在这项研究中,使用QSAR设计潜在的PLpro抑制药物，分子对接,和分子动力学。建立了具有物理化学和Free-Wilson描述符的组合QSAR方程。r2、q2和r2测试值分别为0.833、0.770和0.721。从等式中,发现芳环和碱性氮原子的存在对于获得良好的抗病毒活性是至关重要的。然后，创建了PLpro的C111，Y268和H73的结合位点的一系列结构。发现最好的化合物表现出9.124的pIC50值和~14kcal/mol的对接评分值。通过分子动力学研究证实了化合物在腔中的稳定性。芳基-噻吩Pred14和Pred15表现出大量的稳定接触和良好的相互作用，使它们成为潜在的抗病毒候选物。
