流感病毒药物研究进展

Recent Development for Anti-Influenza Drugs

2009年,甲型H1N1流感病毒引发的全球性流感爆发给予我们一个警示:目前的医疗手段在控制流感病毒传染方面很薄弱。目前,流感的预防和治疗措施主要是流感疫苗。然而,从流感病毒株的识别到疫苗的开发有6个月的滞后期并且疫苗的安全性问题也越来越多被关注,因此使常规流感疫苗预防流感爆发与阻止流感传播的有效性受到严重影响。从短期效果来看,化学药物的治疗在控制流感病毒传染中起着至关重要的作用。目前,临床上用于抗流感病毒的药物只有四个:神经氨酸酶抑制剂奥司他韦和扎那米韦,M2离子通道抑制剂金刚烷胺和金刚乙胺。在2009年流感大爆发,而疫苗未能起效时,神经氨酸酶抑制剂发挥了重要的作用。可是,由于耐药的变异病毒株不断涌现仍然导致这些药物的药效降低。因为我们不能预测未来爆发的流感病毒亚型,所以开发针对所有病毒亚型都有效果的广谱抗流感病毒药物以及推广多种药物治疗是很有必要的。在文章中,我们综述了临床在研的抗病毒药物(长效神经氨酸酶抑制剂,聚合酶抑制剂法匹拉韦[T-705]),以及能够同时作用于病毒(血凝素抑制剂蓝藻抗病毒蛋白-N和噻唑立德)或宿主(司他弗林,硝唑尼特)的临床前药物。

The emergence and global spread of the 2009 pandemic H1N1 influenza virus reminds us that we are limited in the stratcgies avaihlble 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 6 months and concerns regarding vaccine safety are a growing issue leading to vaccination refusal. In the short-term, antiviral therapy is vital to control the spread of intluenza. However, we are currently limited to four licensed anti-influenza drugs： the neuraminidase inhibitors oseltamivir and zanamivir, and the M2 ion-channel inhibitors amantadine and rimantadine. The value of neuraminidase 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. In this article we review the experimental data on investigational antiviral agents undergoing clinical trials （long-acting neuraminidase inhibitors and the polymerase inhibitor favipiravir [T-705]） and experimental antiviral agents that target either the virus （the haemagglutinininhibitor cyanovirin-N and thiazotides） or the host （stachyflin, Nitazoxanide）.