Piperno A, Cordaro M, Scala A, Iannazzo D
Dipartimento di Scienze Chimiche, Universita' degli Studi di Messina, viale F. Stagno D'Alcontres 31, 98166, Messina, Italia.
Curr Med Chem. 2014;21(16):1843-60. doi: 10.2174/0929867321666131228205935.
Research on Hepatitis C Virus inhibitors has dramatically increased during the past few years. Actually, several classes of anti-HCV drugs, including NS3/4A protease inhibitors, NS5B polymerase inhibitors, NS4B protein to RNA binding inhibitors, and multifunctional viral protein NS5A inhibitors, are in different stages of development. The RNA dependent HCV polymerase is considered an irreplaceable target for future HCV therapy on account of a high degree of conservation across the six HCV genotypes, and agents targeting the active site, such as ribonucleoside analogs, may be particularly advantageous having a high barrier to resistance. The purpose of this review is to present highlights of recent developments in the synthesis of anti-HCV ribonucleosides and to discuss the limitations posed by resistance and drug toxicity.
在过去几年中，丙型肝炎病毒抑制剂的研究显著增加。实际上，几类抗丙肝病毒药物，包括NS3/4A蛋白酶抑制剂、NS5B聚合酶抑制剂、NS4B蛋白与RNA结合抑制剂以及多功能病毒蛋白NS5A抑制剂，正处于不同的研发阶段。由于在六种丙肝病毒基因型中具有高度保守性，依赖RNA的丙肝病毒聚合酶被认为是未来丙肝治疗中不可替代的靶点，而靶向活性位点的药物，如核苷类似物，可能因具有高耐药屏障而特别具有优势。本综述的目的是介绍抗丙肝核苷合成的最新进展亮点，并讨论耐药性和药物毒性带来的局限性。
