Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, United States.
Curr Opin Virol. 2011 Dec;1(6):607-16. doi: 10.1016/j.coviro.2011.10.019. Epub 2011 Nov 13.
Several directly acting and host targeting antivirals that inhibit hepatitis C virus replication have entered clinical trials. Among the most advanced of these are RG7128, an inhibitor of the NS5B polymerase; BMS-790052, an inhibitor of NS5A; and alisporivir, an inhibitor of human cyclophilins. These agents have potent antiviral activity in chronic HCV patients, act additively or synergistically with inhibitors of the HCV NS3/4A protease, and improve the rate of virologic response produced by traditional pegylated interferon plus ribavirin therapy. No cross resistance has been observed; moreover, nucleoside NS5B and cyclophilin inhibitors appear to suppress resistance to non-nucleoside NS5B and NS3/4A inhibitors. Several recent reports of virologic responses produced by combinations of agents that inhibit HCV replication in the absence of interferon provide optimism that eradication of HCV will be possible without interferon in the future.
几种直接作用于病毒和宿主靶向的抗 HCV 药物已进入临床试验。其中最先进的有 NS5B 聚合酶抑制剂 RG7128、NS5A 抑制剂 BMS-790052 和人亲环素抑制剂 alisporivir。这些药物在慢性 HCV 患者中具有强大的抗病毒活性，与 HCV NS3/4A 蛋白酶抑制剂具有相加或协同作用，并提高了传统聚乙二醇干扰素加利巴韦林治疗产生的病毒学应答率。尚未观察到交叉耐药性；此外，核苷 NS5B 和亲环素抑制剂似乎抑制了对非核苷 NS5B 和 NS3/4A 抑制剂的耐药性。最近有几项关于无干扰素情况下抑制 HCV 复制的药物联合治疗产生病毒学应答的报告，这让人乐观地认为，未来有可能在不使用干扰素的情况下清除 HCV。
