Identification of a novel inhibitor of influenza virus polymerase based on inhibition of conformational change required for cap-dependent endonuclease activity

流感病毒聚合酶从细胞mRNA切割加帽的RNA片段，并用作启动病毒转录的引物，其产生加帽的病毒mRNA分子。 这种独特的机制是发现抗流感疗法的目标。 在这项研究中，我们研究了这种酶的构象变化所需的内切酶活性，并筛选酶抑制剂的基础上抑制所确定的构象变化。 我们确定了蛋白质区域显示的构象变化后，帽结合和两个小的化合物作为这种变化和帽依赖性核酸内切酶活性的抑制剂。

Influenza viral polymerase cleaves capped RNA fragments from cellular mRNAs and uses as primers for initiating viral transcription, which generates capped viral mRNA molecules. This unique mechanism is a target for the discovery of anti-influenza therapeutics. In this study, we investigated a conformational change of this enzyme required for the endonuclease activity, and screened enzymatic inhibitor based on inhibition of the identified conformational change. We identified the protein region showing the conformational change upon cap-binding and two small compounds as an inhibitor of both this change and cap-dependent endonuclease activity.