The influenza virus RNA-dependent RNA polymerase is highly conserved among influenza A, B, C, and D viruses. It comprises three subunits: polymerase basic protein 1 (PB1), polymerase basic protein 2 (PB2), and polymerase acidic protein (PA) in influenza A and B viruses or polymerase 3 protein (P3) in influenza C and D viruses. Because this polymerase is essential for influenza virus replication, it has been considered as a target for antiviral agents. Recently, several polymerase inhibitors that target each subunit have been developed. This review discusses the mechanism of action, antiviral activity, and emergence of resistance to three inhibitors approved for the treatment of influenza or in late-phase clinical trials: the PB1 inhibitor favipiravir, the PB2 inhibitor pimodivir, and the PA inhibitor baloxavir marboxil.

中文翻译：

---

流感聚合酶抑制剂：作用和抗性机制

甲型，乙型，丙型和丁型流感病毒中，流感病毒RNA依赖性RNA聚合酶高度保守。它包含三个亚基：甲型和乙型流感病毒中的聚合酶碱性蛋白1（PB1），聚合酶碱性蛋白2（PB2）和聚合酶酸性蛋白（PA），或丙型和丁型流感病毒中的聚合酶3蛋白（P3）。由于该聚合酶对于流感病毒复制至关重要，因此已被视为抗病毒药物的靶标。最近，已经开发了几种靶向每个亚基的聚合酶抑制剂。这篇综述讨论了三种机制的作用机理，抗病毒活性以及对已批准用于治疗流感或晚期临床试验的抑制剂的耐药性的出现：PB1抑制剂favipiravir，PB2抑制剂pimodivir和PA抑制剂baloxavir marboxil。