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首页> 外文期刊>Antiviral chemistry & chemotherapy >Progress in the discovery of compounds inhibiting orthopoxviruses in animal models.
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Progress in the discovery of compounds inhibiting orthopoxviruses in animal models.

机译：在动物模型中发现抑制正痘病毒的化合物的进展。

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Surrogate animal models must be used for testing antiviral agents against variola (smallpox) virus infections. Once developed, these, compounds can be stockpiled for use in the event of a bioterrorist incident involving either variola or monkeypox virus, or used to treat an occasional serious orthopoxvirus infection, such as disseminated vaccinia complication following exposure to the live virus vaccine. Recently, considerable progress has been made in the discovery of novel antiviral agents found active against orthopoxviruses in vivo. This includes the development of new animal models or refinement of existing ones for compound efficacy testing. Current mouse models employ ectromelia, cowpox and vaccinia (WR and IHD strains) viruses with respiratory (lung) or tail lesion infections commonly studied. Rabbitpox and vaccinia (WR strain) viruses are available for rabbit infections. Monkeypox and variola viruses are used for infecting monkeys. This review describes these and other animal models, and covers compounds found active in vivo from 2003 to date. Cidofovir, known to be active against orthopox virus infections prior to 2003, has been studied extensively over recent years. New compounds showing promise are orally active inhibitors of orthopoxvirus infections that include ether lipid prodrugs of cidofovir and (S)-HPMPA, ST-246, N-methanocarbathymidine (N-MCT) and SRI 21950 (a 4'-thio derivative of iododeoxyuridine). Another compound with high activity but requiring parenteral administration is HPMPO-DAPy. Further development of these compounds is warranted.
机译：必须使用替代动物模型来测试抗天花病毒感染的抗病毒药物。一旦开发成功，这些化合物就可以储存起来，用于发生天花病毒或猴痘病毒的生物恐怖事件，或用于治疗偶发性正痘病毒的偶然严重感染，例如暴露于活病毒疫苗后的弥漫性牛痘并发症。近来，在发现在体内对正痘病毒具有活性的新型抗病毒剂方面已取得相当大的进展。这包括开发新的动物模型或改进现有动物模型以进行复合功效测试。当前的小鼠模型使用了常见的研究有呼吸道（肺）或尾部病变感染的念珠菌，牛痘和牛痘（WR和IHD株）病毒。兔痘和牛痘（WR株）病毒可用于兔感染。猴痘和天花病毒用于感染猴子。这篇综述描述了这些动物模型和其他动物模型，并涵盖了从2003年至今在体内具有活性的化合物。已知在2003年前具有抗正痘病毒感染活性的西多福韦已被广泛研究。具有前景的新化合物是正痘病毒感染的口服活性抑制剂，包括西多福韦和（S）-HPMPA，ST-246，N-甲氨基甲硫咪啶（N-MCT）和SRI 21950（碘脱氧尿苷的4'-硫衍生物）的醚脂质前药。具有高活性但需要肠胃外给药的另一种化合物是HPMPO-DAPy。这些化合物有待进一步开发。

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