（R）-9-（2-膦酰甲氧基丙基）-2,6-二氨基嘌呤是猫免疫缺陷病毒感染的有效抑制剂。
(R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine is a potent inhibitor of feline immunodeficiency virus infection.
作者信息
Vahlenkamp T W, De Ronde A, Balzarini J, Naesens L, De Clercq E, van Eijk M J, Horzinek M C, Egberink H F
机构信息
Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.
出版信息
Antimicrob Agents Chemother. 1995 Mar;39(3):746-9. doi: 10.1128/AAC.39.3.746.
Abstract
The antiviral efficacy of acyclic nucleoside phosphonates, including 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and (R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine [(R)-PMPDAP] against feline immunodeficiency virus (FIV) infection was determined. (R)-PMPDAP showed the highest selectivity index (> 2,000) in vitro. Treatment of experimentally FIV-infected asymptomatic cats with PMEA or (R)-PMPDAP had no effect on the CD4+/CD8+ ratio. However, mean plasma viral RNA concentrations decreased significantly in the (R)-PMPDAP-treated cats. Our data show that, in comparison to PMEA, (R)-PMPDAP is a more potent and less toxic inhibitor of FIV replication both in vitro and in vivo.
摘要
测定了包括9-(2-膦酰甲氧基乙基)腺嘌呤（PMEA）和（R）-9-(2-膦酰甲氧基丙基)-2,6-二氨基嘌呤[(R)-PMPDAP]在内的无环核苷膦酸酯对猫免疫缺陷病毒（FIV）感染的抗病毒效力。（R）-PMPDAP在体外显示出最高的选择性指数（>2000）。用PMEA或（R）-PMPDAP治疗实验性感染FIV的无症状猫对CD4+/CD8+比值没有影响。然而，在接受（R）-PMPDAP治疗的猫中，血浆病毒RNA平均浓度显著降低。我们的数据表明，与PMEA相比，（R）-PMPDAP在体外和体内都是一种更有效且毒性更小的FIV复制抑制剂。
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本文引用的文献
1
Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates: potent and selective in vitro and in vivo antiretrovirus activities of (R)-9-(2-phosphonomethoxypropyl)-2,6-diaminopurine.无环核苷膦酸酯的（S）和（R）对映体的抗疱疹病毒和抗逆转录病毒差异效应：（R）-9-（2-膦酰甲氧基丙基）-2,6-二氨基嘌呤在体外和体内具有高效且选择性的抗逆转录病毒活性。
Antimicrob Agents Chemother. 1993 Feb;37(2):332-8. doi: 10.1128/AAC.37.2.332.
2
Detection of feline immunodeficiency virus in saliva and plasma by cultivation and polymerase chain reaction.通过培养和聚合酶链反应检测唾液和血浆中的猫免疫缺陷病毒。
J Clin Microbiol. 1993 Mar;31(3):494-501. doi: 10.1128/jcm.31.3.494-501.1993.
3
Prophylactic ZDV therapy prevents early viremia and lymphocyte decline but not primary infection in feline immunodeficiency virus-inoculated cats.预防性齐多夫定（ZDV）治疗可预防猫免疫缺陷病毒接种猫的早期病毒血症和淋巴细胞减少，但不能预防原发性感染。
J Acquir Immune Defic Syndr (1988). 1993 Feb;6(2):127-34.
4
High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR.通过竞争性聚合酶链反应确定，在感染的所有阶段血浆中均存在高水平的HIV-1。
Science. 1993 Mar 19;259(5102):1749-54. doi: 10.1126/science.8096089.
5
Measurement of HIV virus load and genotypic resistance by gene amplification in asymptomatic subjects treated with combination therapy.采用基因扩增法对接受联合治疗的无症状受试者进行HIV病毒载量及基因型耐药性检测。
J Acquir Immune Defic Syndr (1988). 1993 Apr;6(4):366-9.
6
Isolation of a T-lymphotropic virus from domestic cats with an immunodeficiency-like syndrome.从患有类似免疫缺陷综合征的家猫中分离出一种嗜T淋巴细胞病毒。
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7
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8
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9
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10
Epidemiologic and clinical aspects of feline immunodeficiency virus infection in cats from the continental United States and Canada and possible mode of transmission.
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