School of Pharmacy, Bharat Institute of Technology, Partapur, Meerut-250 103 (UP), India.
Curr Med Chem. 2011;18(36):5564-97. doi: 10.2174/092986711798347234.
Hepatitis C virus (HCV) infection has emerged as one of the most significant disease to affect humans. Despite its large medical and economical impact, there are no vaccines or efficient therapies without major side effects. The HCV non-structural protein 5B (NS5B) is the RNA-dependent RNA polymerase responsible for the complete copy of the RNA viral genome and is a target of choice for the development of anti-HCV drugs. Although many small molecules have been identified as allosteric inhibitors of NS5B, very few are active in clinical applications. Developments in the field have prompted us to review the research work on HCV NS5B polymerase inhibitors, especially their structure activity relationships and molecular modeling studies. This review will focus on the journey of drug discovery of HCV NS5B inhibitors covering both nucleoside and non-nucleosides.
丙型肝炎病毒(HCV)感染已成为影响人类的最重要疾病之一。尽管它具有重大的医学和经济影响,但仍没有没有重大副作用的疫苗或有效疗法。丙型肝炎非结构蛋白 5B(NS5B)是负责 RNA 病毒基因组完整复制的 RNA 依赖性 RNA 聚合酶,是开发抗 HCV 药物的首选靶标。尽管已经鉴定出许多小分子作为 NS5B 的别构抑制剂,但很少有在临床应用中具有活性。该领域的发展促使我们回顾丙型肝炎 NS5B 聚合酶抑制剂的研究工作,特别是它们的结构活性关系和分子建模研究。本综述将重点介绍 HCV NS5B 抑制剂的药物发现之旅,涵盖核苷和非核苷类药物。