The propensity of influenza virus to develop resistance to commonly prescribed drugs highlights the need for continuing development of new therapeutics. Biological and structural investigations of the enzymatic and interaction domains among influenza A virus polymerase subunits have broadened the target reservoir for drug screening. With the wealth of knowledge from these studies, identification of small-molecule and peptidic inhibitors that specifically abrogate polymerase activity or disrupt the polymerase assembly has emerged as an innovative and promising approach. Importantly, those domains are highly conserved among influenza subtypes and thus minimize the emergence of drug resistant mutants. An overview of the reported enzymatic inhibitors and protein–protein disruptors has been provided, in our effort to facilitate the development of next-generation anti-influenza therapeutics.

中文翻译：

---

甲型流感病毒聚合酶抑制剂

流感病毒对常用处方药产生抗药性的倾向凸显了持续开发新疗法的必要性。甲型流感病毒聚合酶亚基之间酶和相互作用域的生物学和结构研究扩大了药物筛选的目标库。利用这些研究中的大量知识，鉴定特异性消除聚合酶活性或破坏聚合酶装配的小分子和肽类抑制剂已成为一种创新且有前途的方法。重要的是，这些结构域在流感亚型中是高度保守的，因此使耐药突变体的出现最小化。提供了已报道的酶促抑制剂和蛋白质-蛋白质破坏剂的概述，