Molecular strategies to inhibit the replication of RNA viruses.
Molecular strategies to inhibit the replication of RNA viruses.
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DOI：
10.1016/j.antiviral.2008.01.004
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发表时间：
2008-04
影响因子：
7.6
通讯作者：
Neyts J
中科院分区：
文献类型：
--
作者：
Leyssen P;De Clercq E;Neyts J
几乎没有抗病毒药物可用于治疗RNA病毒感染。这一点特别令人担忧，因为大多数高致病性和新出现的病毒都是，而且很可能继续是RNA病毒。这些病毒可引起急性严重疾病，包括严重呼吸道疾病、出血热和脑炎，病死率很高。重要的是手头有可以用于治疗或预防这种感染的有效和安全的药物。被批准用于治疗RNA病毒感染(艾滋病毒除外)的药物有流感M2通道抑制剂金刚烷胺和金刚乙胺；流感神经氨酸酶抑制剂奥司他韦和扎那米韦，以及用于治疗呼吸道合胞病毒和丙型肝炎病毒感染的利巴韦林。利巴韦林抑制病毒复制的分子机制(S)，如耗尽细胞内GTP池和诱导错误灾难，可能不容易设计出比母药更有效/更有选择性的类似物。高致病性RNA病毒属于多种病毒家族，每个家族都有特定的复制策略，因此提供了大量的潜在靶点来选择性地抑制病毒复制。我们在这里提供一个非穷尽的审查潜在的实验策略，使用小分子，以抑制几种RNA病毒的复制。其他方法，如使用干扰素或其他宿主反应调节剂、免疫血清或中和抗体，不在本综述中讨论。
There are virtually no antiviral drugs available for the treatment of infections with RNA viruses. This is particularly worrisome since most of the highly pathogenic and emerging viruses are, and will likely continue to be, RNA viruses. These viruses can cause acute, severe illness, including severe respiratory disease, hemorrhagic fever and encephalitis, with a high case fatality rate. It is important to have potent and safe drugs at hand that can be used for the treatment or prophylaxis of such infections. Drugs approved for the treatment of RNA virus infections (other than HIV) are the influenza M2 channel inhibitors, amantadine and rimantadine; the influenza neuraminidase inhibitors, oseltamivir and zanamivir, and ribavirin for the treatment of infections with respiratory syncytial virus and hepatitis C virus. The molecular mechanism(s) by which ribavirin inhibits viral replication, such as depletion of intracellular GTP pools and induction of error catastrophe, may not readily allow the design of analogues that are more potent/selective than the parent drug. Highly pathogenic RNA viruses belong to a variety of virus families, each having a particular replication strategy, thus offering a wealth of potential targets to selectively inhibit viral replication. We here provide a non-exhaustive review of potential experimental strategies, using small molecules, to inhibit the replication of several RNA viruses. Other approaches, such as the use of interferon or other host-response modifiers, immune serum or neutralizing antibodies, are not addressed in this review.
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