Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan,Pakistan.
Comb Chem High Throughput Screen. 2022;25(2):335-346. doi: 10.2174/1386207323666201228160224.
Hepatitis C Virus (HCV) is one of the serious health issues affecting onethird of the world's population. The high variations of the HCV genome are ascribed to quick replication by NS5B polymerase and are thus the most attractive target for developing anti-HCV agents.
The current study aimed to discover novel phytochemicals that harbor the potential of NS5B polymerase inhibition.
In this computational study, a molecular docking approach was used to screen phytochemicals with the best binding and spatial affinity with NS5B at the Palm I region. The topranked compounds were then subjected to an in-silico pharmacokinetic and toxicological study.
The virtual screening provided seven 'hit compounds' including Betanin, 3,5'- dihydroxythalifaboramine, Diarctigenin, 6'-desmethylthalifaboramine, Cephalotaxine, 5alpha-O- (3'-dimethylamino-3'-phenylpropionyl) taxinine M and IsoTetrandrine with minimum binding score compared to the reference drug, sofosbuvir (-14.7 kcal/mol). The absorption, distribution, metabolism, excretion, and toxicity (ADMET) and thorough toxicological analysis revealed a favorable safety profile of these compounds.
The study demonstrates the identified phytochemicals. These may serve as potential antiviral compounds that can provide an alternative approach for amelioration of HCV.
丙型肝炎病毒 (HCV) 是影响全球三分之一人口的严重健康问题之一。HCV 基因组的高度变异性归因于 NS5B 聚合酶的快速复制，因此是开发抗 HCV 药物的最具吸引力的目标。
本研究旨在发现具有 NS5B 聚合酶抑制潜力的新型植物化学物质。
在这项计算研究中，使用分子对接方法筛选与 NS5B 在 Palm I 区域具有最佳结合和空间亲和力的植物化学物质。然后对排名最高的化合物进行计算机药代动力学和毒理学研究。
虚拟筛选提供了七种“命中化合物”，包括甜菜碱、3,5'-二羟基他拉福林、二氢齿果酸、6'-去甲基他拉福林、石杉碱甲、5α-O-（3'-二甲氨基-3'-苯丙酰基）他可宁 M 和异紫堇定，与参比药物索非布韦（-14.7 kcal/mol）相比，其结合评分最低。吸收、分布、代谢、排泄和毒性 (ADMET) 以及全面的毒理学分析显示这些化合物具有良好的安全性。
该研究表明鉴定出的植物化学物质可能作为潜在的抗病毒化合物，为改善 HCV 提供一种替代方法。
