WHO Collaborating Centre for Reference and Research on Influenza, Melbourne, Victoria, Australia.
Drugs. 2009;69(18):2523-31. doi: 10.2165/11531450-000000000-00000.
Along with influenza vaccines, the world is currently almost completely dependent on two licensed drugs for the treatment or prevention of seasonal (influenza A and B viruses) and pandemic influenza (influenza A viruses). These drugs - oseltamivir (Tamiflu) and zanamivir (Relenza) - are classified as neuraminidase inhibitors (NAIs) because they act by inhibiting one of the key surface proteins of the influenza virus, the neuraminidase, which in turn reduces the ability of the virus to infect other respiratory cells. Our dependence on these drugs has arisen because of high levels of resistance with seasonal influenza viruses to the older class of anti-influenza drugs, the adamantanes (amantadine and rimantadine), combined with the lack of activity of these drugs against influenza B viruses. Recently, however, significant levels of oseltamivir-resistant influenza A(H1) seasonal influenza viruses have also been encountered, which has been associated with a single amino acid change in the viral neuraminidase (H274Y). Oseltamivir is the most widely used and stockpiled NAI and, while these A(H1) viruses are still sensitive to zanamivir, it highlights the ease with which the influenza virus can mutate and reassort to circumvent available drugs. Fortunately, the current pandemic A(H1N1) 2009 virus, which is circulating globally, remains largely sensitive to both NAIs, although a small number of oseltamivir-resistant viruses have been isolated from patients to date, again with the H274Y mutation. Clearly there is a need to use the NAI drugs prudently to ensure they remain an effective defence against future seasonal and pandemic influenza viruses, along with careful monitoring of levels of resistance in the circulating viruses combined with the further development of new anti-influenza drugs.
除流感疫苗外，目前全球几乎完全依赖两种已获许可的药物来治疗或预防季节性（甲型和乙型流感病毒）和大流行性（甲型流感病毒）流感：奥司他韦（达菲）和扎那米韦（瑞乐沙）。这些药物属于神经氨酸酶抑制剂（NAI），因为它们通过抑制流感病毒的一种关键表面蛋白——神经氨酸酶来发挥作用，从而降低病毒感染其他呼吸道细胞的能力。我们对这些药物的依赖源于季节性流感病毒对旧类抗流感药物金刚烷胺（金刚烷胺和金刚乙胺）的高水平耐药性，再加上这些药物对乙型流感病毒缺乏活性。然而，最近也发现了具有高水平奥司他韦耐药性的季节性甲型流感（H1N1）病毒，这与病毒神经氨酸酶（H274Y）的单一氨基酸变化有关。奥司他韦是应用最广泛和库存最多的 NAI，虽然这些甲型（H1）病毒对扎那米韦仍然敏感，但它突出了流感病毒很容易发生突变和重配以规避现有药物。幸运的是，目前在全球传播的大流行甲型（H1N1）2009 病毒对两种 NAI 仍然基本敏感，尽管迄今为止已从患者中分离出少数奥司他韦耐药病毒，同样具有 H274Y 突变。显然，需要谨慎使用 NAI 药物，以确保它们仍然是针对未来季节性和大流行性流感病毒的有效防御手段，同时结合对循环病毒耐药水平的仔细监测以及进一步开发新的抗流感药物。
