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通过抑制病毒的神经氨酸酶来控制流感。

Controlling influenza by inhibiting the virus's neuraminidase.

作者信息

Garman Elspeth, Laver Graeme

机构信息

Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.

出版信息

Curr Drug Targets. 2004 Feb;5(2):119-36. doi: 10.2174/1389450043490604.

Abstract

Despite the fact that influenza is a disease which affects millions of people, sometimes with fatal consequences. there has not, until recently, been any drug effective against all strains. Vaccines may be relatively or totally ineffective, so drugs are needed. Random screening of many thousands of compounds by pharmaceutical companies has resulted in only two compounds, amantadine and rimantidine, which target the M2 ion channel on the virus. These drugs have major disadvantages. Knowledge of the crystal structure of influenza virus neuraminidase, on the other hand, has allowed the rational design of four "plug-drugs" which bind to the active site of flu neuraminidase and stop replication of the virus. Two of these compounds. Relenza and Tamiflu, are now being used worldwide and, although effective when used properly, suffer from problems of delivery. They need to be given very soon after infection to be effective, they only inhibit the influenza virus and none of the other respiratory agents which cause flu-like symptoms, and they are very expensive.

摘要

尽管流感是一种影响数百万人的疾病,有时甚至会导致致命后果,但直到最近,还没有任何一种药物能有效对抗所有毒株。疫苗可能相对无效或完全无效,因此需要药物。制药公司对数以千计的化合物进行随机筛选,仅得到两种靶向病毒上M2离子通道的化合物,即金刚烷胺和金刚乙胺。这些药物有严重的缺点。另一方面,对流感病毒神经氨酸酶晶体结构的了解使得人们能够合理设计出四种与流感神经氨酸酶活性位点结合并阻止病毒复制的“插入式药物”。其中两种化合物,即瑞乐沙和达菲,目前正在全球范围内使用,尽管使用得当会有效果,但存在给药方面的问题。它们需要在感染后尽快给药才能有效,它们只抑制流感病毒,而对其他引起流感样症状的呼吸道病原体无效,而且它们非常昂贵。

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