Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
Rev Med Virol. 2012 Nov;22(6):392-411. doi: 10.1002/rmv.1727. Epub 2012 Aug 30.
After a decade of having been the standard of care (SOC) for the treatment of chronic HCV infection, PEGylated IFN (combined with ribavirin) is now at the verge of being complemented and then replaced by a combination of new DAAs and even some compounds interacting with host cell factors. Principal targets for the direct-acting antivirals (DAAs) are the protease NS3/4A, the protein NS5A, and the RNA-dependent RNA polymerase NS5B, which offers at least two target sites, the catalytic domain for nucleos(t)ides and several non-catalytic (allosteric) domains for the non-nucleoside type of NS5B inhibitors. Two PIs have already been approved, but many more NS3/4A, NS5A, and NS5B (up to 40!) inhibitors are in (pre)clinical development. The abundance of candidate anti-HCV drugs will, on the one hand, speed up their development but, on the other hand, complicate the choice of the most appropriate drug combination(s).
聚乙二醇干扰素（联合利巴韦林）作为慢性 HCV 感染治疗的标准护理（SOC）已长达十年，如今正处于被新的直接作用抗病毒药物（DAAs）组合甚至一些与宿主细胞因子相互作用的化合物补充和替代的边缘。直接作用抗病毒药物（DAAs）的主要靶标是蛋白酶 NS3/4A、蛋白 NS5A 和 RNA 依赖性 RNA 聚合酶 NS5B，它至少提供了两个靶位，一个是核苷酸的催化结构域，以及非核苷类 NS5B 抑制剂的几个非催化（变构）结构域。已经批准了两种蛋白酶抑制剂，但更多的 NS3/4A、NS5A 和 NS5B（多达 40 种！）抑制剂正在（临床前）开发中。候选抗 HCV 药物的丰富性一方面将加快其开发速度，但另一方面也会使选择最合适的药物组合变得复杂。
