The era of interferon-free antiviral treatments for hepatitis C virus infection has arrived. With increasing numbers of approved antivirals, evaluating all parameters that may influence response is necessary to choose optimal combinations for treatment success. Targeting NS5A has become integral in antiviral combinations in clinical development. Daclatasvir and ledipasvir belong to the NS5A inhibitor class, which directly target the NS5A protein. Alisporivir, a host-targeting antiviral, is a cyclophilin inhibitor that indirectly targets NS5A by blocking NS5A/cyclophilin A interaction. Resistance to daclatasvir and ledipasvir differs from alisporivir, with mutations arising in NS5A domains I and II, respectively. Combining these two classes acting on distinct NS5A domains represents an attractive strategy for potentially effective interferon-free treatments for chronic hepatitis C infection.

丙型肝炎病毒感染的无干扰素抗病毒治疗时代已经到来。随着批准的抗病毒药物数量的增加，评估可能影响反应的所有参数对于选择治疗成功的最佳组合是必要的。靶向 NS5A 已成为临床开发中抗病毒组合的组成部分。Daclatasvir 和 ledipasvir 属于 NS5A 抑制剂类，直接靶向 NS5A 蛋白。Alisporivir 是一种靶向宿主的抗病毒药物，是一种亲环蛋白抑制剂，通过阻断 NS5A/亲环蛋白 A 相互作用间接靶向 NS5A。对 daclatasvir 和 ledipasvir 的耐药性与 alisporivir 不同，分别在 NS5A 结构域 I 和 II 出现突变。