Influenza is an acute respiratory infectious disease caused by the influenza virus, affecting people globally and causing significant social and economic losses. Due to the inevitable limitations of vaccines and approved drugs, there is an urgent need to discover new anti-influenza drugs with different mechanisms. The viral ribonucleoprotein complex (vRNP) plays an essential role in the life cycle of influenza viruses, representing an attractive target for drug design. In recent years, the functional area of constituent proteins in vRNP are widely used as targets for drug discovery, especially the PA endonuclease active site, the RNA-binding site of PB1, the cap-binding site of PB2 and the nuclear export signal of NP protein. Encouragingly, the PA inhibitor baloxavir has been marketed in Japan and the United States, and several drug candidates have also entered clinical trials, such as favipiravir. This article reviews the compositions and functions of the influenza virus vRNP and the research progress on vRNP inhibitors, and discusses the representative drug discovery and optimization strategies pursued.

流感是由流感病毒引起的急性呼吸道传染病，影响全球人群，造成重大社会和经济损失。由于疫苗和获批药物的不可避免的局限性，迫切需要发现具有不同作用机制的新型抗流感药物。病毒核糖核蛋白复合物 (vRNP) 在流感病毒的生命周期中起着至关重要的作用，是药物设计的一个有吸引力的目标。近年来，vRNP中组成蛋白的功能区被广泛用作药物发现的靶点，尤其是PA内切酶活性位点、PB1的RNA结合位点、PB2的帽结合位点和NP的核输出信号。蛋白质。令人鼓舞的是，PA抑制剂巴洛沙韦已在日本和美国上市，还有几个候选药物也进入了临床试验，比如法匹拉韦。本文回顾了流感病毒 vRNP 的组成和功能以及 vRNP 抑制剂的研究进展，并讨论了具有代表性的药物发现和优化策略。