Confronting an influenza pandemic with inexpensive generic agents: can it be done?
Confronting an influenza pandemic with inexpensive generic agents: can it be done?
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DOI：
10.1016/s1473-3099(08)70070-7
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发表时间：
2008-09
期刊：
影响因子：
--
通讯作者：
Fedson DS
中科院分区：
文献类型：
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作者：
Fedson DS
H5N1禽流感是一种严重的、可能迫在眉睫的大流行威胁。在这种情况下，世界上大多数人将无法获得足够的负担得起的疫苗和抗病毒剂。鉴于对有效替代品的迫切需求，应考虑针对宿主免疫反应或大流行性病毒的仿制药。许多科学家怀疑这些药物的有效性。尽管如此，一些研究表明，他汀类药物改善了菌血症和肺炎患者的预后，对流感也可能同样有效。一项实验研究表明，贝特吉非贝齐（一种过氧化物酶体增殖物激活受体（PPAR）α激动剂）可降低H2N2流感病毒感染小鼠的死亡率。他汀类药物和过氧化物酶体增殖物激活受体激动剂之间存在大量的分子串扰，它们在心血管疾病患者中的临床作用是相加的。氯喹增加内体pH，削弱流感病毒释放到胞质溶胶。他汀类药物、贝特类药物和氯喹在发展中国家作为非专利药物生产。这些疫苗价格低廉，可以储存起来，在大流行的第一天就可以使用。由于缺乏现实的替代品来应对下一次大流行，迫切需要进行研究，以确定这些药物和其他非专利药物是否可以减轻可能成为前所未有的全球公共卫生危机的影响。
Avian influenza A H5N1 presents a serious and possibly imminent pandemic threat. In such an event, adequate supplies of affordable vaccines and antiviral agents will be unavailable to most people in the world. In view of the overwhelming need for effective alternatives, generic agents that target the host immune response or the pandemic virus should be considered. Many scientists doubt the effectiveness of these agents. Nonetheless, several studies suggest that statins improve outcomes in patients with bacteraemia and pneumonia and might be similarly effective against influenza. An experimental study has shown that the fibrate gemfibrozil, a peroxisome proliferator-activated receptor (PPAR) α agonist, reduces mortality in H2N2 influenza virus-infected mice. There is substantial molecular cross-talk between statins and PPAR agonists, and their clinical effects are additive in patients with cardiovascular diseases. Chloroquine increases endosomal pH, impairing influenza virus release into the cytosol. Statins, fibrates, and chloroquine are produced as generic medications in developing countries. They are inexpensive, could be stockpiled, and would be available on the first pandemic day. With a lack of realistic alternatives for confronting the next pandemic, research is urgently needed to determine whether these and other generic agents could mitigate the effects of what might otherwise become an unprecedented global public-health crisis.