Drugs in development for influenza.
Drugs in development for influenza.
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DOI：
10.2165/11537960-000000000-00000
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发表时间：
2010-07-30
期刊：
影响因子：
11.5
通讯作者：
Govorkova EA
中科院分区：
文献类型：
--
作者：
Boltz DA;Aldridge JR Jr;Webster RG;Govorkova EA
2009年H1N1流感大流行病毒的出现和全球传播提醒我们，我们控制流感感染的现有战略有限。疫苗是预防和控制大流行的最佳选择；然而，病毒鉴定和疫苗分发之间的滞后时间超过6个月，对疫苗安全性的担忧日益成为导致拒绝接种疫苗的问题。在短期内，抗病毒治疗对控制流感的传播至关重要；然而，我们目前仅限于四种已获批的抗流感药物：神经氨酸酶（NA）抑制剂奥司他韦和扎那米韦，以及M2离子通道抑制剂金刚烷胺和金刚乙胺。在2009年大流行的初始阶段，当没有疫苗时，NA抑制剂的价值得到了明确确立，即抗病毒药物的储备是有价值的。不幸的是，随着耐药变异继续自然出现，并通过使用抗病毒药物施加的选择性压力，这些药物的功效下降。由于我们无法预测将导致下一次流感流行或大流行的流感病毒株，因此开发对所有菌株和亚型具有广泛反应性的新型抗流感药物并考虑在未来转向多种药物治疗是很重要的。在这里，我们回顾了正在进行临床试验的研究性抗病毒药物的实验数据[静脉注射扎那米韦和帕拉米韦；长效NA抑制剂（LANI）和聚合酶抑制剂T-705]，针对病毒[血凝素（HA）抑制剂Cyanovirin-N和Thiazolides]或宿主[融合蛋白抑制剂（DAS181）， Cox-2抑制剂和PPAR激动剂]的实验性抗病毒药物。
The emergence and global spread of the 2009 pandemic H1N1 influenza virus reminds us that we are limited in the strategies available to control influenza infection. Vaccines are the best option for the prophylaxis and control of a pandemic; however the lag time between virus identification and vaccine distribution exceeds six months and concerns of vaccine safety are a growing issue leading to vaccination refusal. In the short term, antiviral therapy is vital to control the spread of influenza; however, we are currently limited to four licensed anti-influenza drugs: the neuraminidase (NA) inhibitors oseltamivir and zanamivir, and M2 ion-channel inhibitors amantadine and rimantadine. The value of NA inhibitors was clearly established during the initial phases of the 2009 pandemic when vaccines were not available, i.e. stockpiles of antivirals are valuable. Unfortunately, as drug-resistant variants continue to emerge naturally and through selective pressure applied by use of antiviral drugs, the efficacy of these drugs declines. Because we cannot predict the strain of influenza virus that will cause the next epidemic or pandemic, it is important that we develop novel anti-influenza drugs with broad reactivity against all strains and subtypes and consider moving to multiple drug therapy in the future. Here we review the experimental data on investigational antiviral agents undergoing clinical trials [parenteral zanamivir and peramivir; long acting NA inhibitors (LANI), and polymerase inhibitor T-705], experimental antiviral agents that target either the virus [hemagglutinin (HA) inhibitor Cyanovirin-N and Thiazolides] or the host [fusion protein inhibitor (DAS181), Cox-2 inhibitors and PPAR agonists].
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