靶向流感病毒RNA依赖的RNA聚合酶的小分子抑制剂研究进展

Recent advances in small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase

流感病毒严重威胁人类的生命健康。由于流感病毒固有的高变异性,目前上市的抗流感病毒药物已出现临床耐药突变株。因此,亟需开发具有新靶标、新机制的抗流感药物。RNA依赖的RNA聚合酶直接负责病毒RNA的转录和复制,在病毒的生命周期中发挥关键作用,是抗流感药物的重要靶标。本文精选近十年典型研究实例,从药物化学角度总结了靶向流感病毒RNA依赖的RNA聚合酶抑制剂的研究进展,以期为研发抗流感病毒药物提供参考。

Influenza virus causes serious threat to human life and health.Due to the inherent high variability of influenza virus,clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged.Therefore,it is urgent to develop antiviral drugs with new targets or mechanisms of action.RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication,and plays key roles in the viral life cycle,which is considered an important target of anti-influenza drug design.From the point of view of medicinal chemistry,this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase,hoping to provide valuable reference for development of novel antiviral drugs.