In vitro evaluation of the anti-orf virus activity of alkoxyalkyl esters of CDV, cCDV and (S)-HPMPA
In vitro evaluation of the anti-orf virus activity of alkoxyalkyl esters of CDV, cCDV and (S)-HPMPA
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DOI：
10.1016/j.antiviral.2006.11.010
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发表时间：
2007-07-01
影响因子：
7.6
通讯作者：
Snoeck, Robert
中科院分区：
文献类型：
--
作者：
Dal Pozzo, Fabiana;Andrei, Graciela;Snoeck, Robert
无环核苷膦酸酯（ANP），特别是（S）-1-[3-羟基-2-（膦酰甲氧基）丙基]胞嘧啶（HPMPC，西多福韦，CDV，Vistide（R））及其腺嘌呤对应物（S）-9-[3-羟基-2-（膦酰甲氧基）丙基]腺嘌呤[（S）-HPMPA]对牛痘病毒感染具有高度活性。这种副痘病毒通常会引起绵羊、山羊和人类的感染。CDV的烷氧基烷基酯具有增加的口服生物利用度，并且比母体化合物对正痘病毒更有活性。在本研究中，评价了CDV的几种烷氧基烷基酯、环西多福韦（cCDV）和（S）-HPMPA在两种细胞类型（人胚肺（HEL）成纤维细胞和原代羔羊角质形成细胞）中针对不同的羊口疮病毒分离株的效力。每种前药在两种细胞类型中的活性至少是其母体化合物的10倍。在所有测试的化合物中，（S）-HPMPA烷氧基烷基酯显示出最高的抗羊口疮病毒的活性和选择性。我们的研究结果支持开发的烷氧基烷基酯的ANP作为抗病毒药物，不仅用于治疗复杂的人类orf病变，但也在治疗和预防传染性脓疱的绵羊和山羊。(C)2006 Elsevier B. V.保留所有权利。
Acyclic nucleoside phosphonates (ANPs) and in particular (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC, cidofovir, CDV, Vistide (R)) and its adenine counterpart (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl] adenine [(S)-HPMPA] are highly active against orf virus infections. This parapoxvirus commonly causes infection in sheep, goats, but also humans. Alkoxyalkyl esters of CDV have an increased oral bioavailability and are more active against orthopoxviruses than the parent compounds. In the present study, the potency of several alkoxyalkyl esters of CDV, cyclic cidofovir (cCDV) and (S)-HPMPA was evaluated against different orf virus isolates in two cell types, human embryonic lung (HEL) fibroblast and primary lamb keratinocytes. Each prodrug was at least 10-fold more active than its parent compound in both cell types. Of all the compounds tested, the (S)-HPMPA alkoxyalkyl esters showed the highest activity and selectivity against orf virus. Our results support the development of alkoxyalkyl esters of ANPs as antivirals not only for the treatment of complicated human orf lesions, but also in the therapy and prophylaxis of contagious ecthyma in sheep and goats. (C) 2006 Elsevier B.V. All rights reserved.