School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region.
Curr Opin Virol. 2016 Jun;18:126-34. doi: 10.1016/j.coviro.2016.05.004. Epub 2016 Jun 23.
Influenza A and B viruses are major causes for respiratory infections in children and adults. Viral and host factors determine clinical manifestations which range from self-resolving uncomplicated infections, severe viral or bacterial secondary pneumonia, to death. Emergence of transmissible resistant variants and time-dependent effectiveness are the major challenges for the currently approved antivirals, M2 ion channel blockers and neuraminidase (NA) inhibitors. Favipiravir that inhibits the RNA-dependent RNA polymerase of multiple RNA viruses is approved in Japan against influenza strains resistant to available antivirals. With expanded knowledge on viral nucleoprotein (NP) and polymerase structures, novel small molecule inhibitors targeting NP oligomer formation, PA endonuclease domain, and the PB2 cap-binding domain are being developed. Combination therapy with different antiviral compounds or with host immune response modulators may further benefit clinical outcomes.
甲型和乙型流感病毒是导致儿童和成人呼吸道感染的主要原因。病毒和宿主因素决定了临床表现的范围，从自限性无症状感染、严重的病毒性或细菌性继发性肺炎到死亡不等。可传播的耐药变异体的出现和时间依赖性疗效是目前批准的抗病毒药物、M2 离子通道阻滞剂和神经氨酸酶（NA）抑制剂面临的主要挑战。法匹拉韦可抑制多种 RNA 病毒的 RNA 依赖性 RNA 聚合酶，在日本被批准用于治疗对现有抗病毒药物耐药的流感株。随着对病毒核蛋白（NP）和聚合酶结构的了解不断扩大，针对 NP 寡聚体形成、PA 内切酶结构域和 PB2 帽结合结构域的新型小分子抑制剂正在开发中。不同抗病毒化合物的联合治疗或与宿主免疫反应调节剂的联合治疗可能会进一步改善临床结局。
