Department of Biochemistry, Government College University, Faisalabad, Pakistan.
Pak J Pharm Sci. 2020 Sep;33(5(Supplementary)):2317-2322.
Hepatitis C virus (HCV) has major role in spreading of liver diseases worldwide. The HCV nonstructural NS5B is a polymerase (RdRp) that is present at the carboxylic-end of the polyprotein chain. It is essential and most important for the replication cycle. In current study, the potential of 100 phytochemicals against HCV NS5B polymerase was determined. Phytochemical structures were retrieved from PubChem database. The phytochemicals were docked with the NS5B active site amino acids, in order to discover their attractions as inhibitors. After docking, molecules with top five conformations were selected from 100 molecules by docking scores and RMSD values. The results demonstrated strong interactions of phytochemicals with the NS5B. The selected compounds with best docking scores and RMSD were found to be glycitein, ferulic acid, eugenol, 1-octanol and sebacic acid. These were further evaluated through Lipinski's rule of five to explore their molecular properties and drug-likeliness characteristics and all five selected phytochemicals were found to have drug-likeliness characteristics. Further, according to ADME analysis, the ferulic acid, 1-octanol and eugenol were found to be nontoxic, non-carcinogenic and have the ability to cross the blood brain barriers. Therefore, these phytochemicals could be strong drug candidates for HCV NS5B.
丙型肝炎病毒（HCV）在全球范围内的肝脏疾病传播中起着重要作用。HCV 的非结构 NS5B 是一种聚合酶（RdRp），位于多蛋白链的羧基末端。它对复制周期是必不可少的，也是最重要的。在本研究中，测定了 100 种植物化学物质对 HCV NS5B 聚合酶的潜在作用。植物化学物质的结构从 PubChem 数据库中检索。将植物化学物质与 NS5B 活性位点的氨基酸对接，以发现它们作为抑制剂的吸引力。对接后，根据对接分数和 RMSD 值，从 100 种分子中选择前五个构象的分子。结果表明，植物化学物质与 NS5B 之间存在强烈的相互作用。根据对接分数和 RMSD 值，选择具有最佳对接分数和 RMSD 值的化合物为黄豆苷元、阿魏酸、丁香酚、1-辛醇和癸二酸。通过 Lipinski 的五规则进一步评估这些化合物，以探索它们的分子性质和类药性特征，发现这 5 种植物化学物质均具有类药性特征。此外，根据 ADME 分析，阿魏酸、1-辛醇和丁香酚是非毒性的、非致癌的，并且具有穿过血脑屏障的能力。因此，这些植物化学物质可能是 HCV NS5B 的有效候选药物。
