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抗猫疱疹病毒1的抗病毒药物的体外比较

In vitro comparison of antiviral drugs against feline herpesvirus 1.

作者信息

van der Meulen K, Garré B, Croubels S, Nauwynck H

机构信息

Laboratory of Virology, Faculty of Veterinary Medicine, Salisburylaan 133, Ghent University, 9820 Merelbeke, Belgium.

出版信息

BMC Vet Res. 2006 Apr 26;2:13. doi: 10.1186/1746-6148-2-13.

Abstract

BACKGROUND

Feline herpesvirus 1 (FHV-1) is a common cause of respiratory and ocular disease in cats. Especially in young kittens that have not yet reached the age of vaccination, but already lost maternal immunity, severe disease may occur. Therefore, there is a need for an effective antiviral treatment. In the present study, the efficacy of six antiviral drugs, i.e. acyclovir, ganciclovir, cidofovir, foscarnet, adefovir and 9-(2-phosphonylmethoxyethyl)-2, 6-diaminopurine (PMEDAP), against FHV-1 was compared in Crandell-Rees feline kidney (CRFK) cells using reduction in plaque number and plaque size as parameters.

RESULTS

The capacity to reduce the number of plaques was most pronounced for ganciclovir, PMEDAP and cidofovir. IC50 (NUMBER) values were 3.2 microg/ml (12.5 microM), 4.8 microg/ml (14.3 microM) and 6 microg/ml (21.5 microM), respectively. Adefovir and foscarnet were intermediately efficient with an IC50 (NUMBER) of 20 microg/ml (73.2 microM) and 27 microg/ml (140.6 microM), respectively. Acyclovir was least efficient (IC50 (NUMBER) of 56 microg/ml or 248.7 microM). All antiviral drugs were able to significantly reduce plaque size when compared with the untreated control. As observed for the reduction in plaque number, ganciclovir, PMEDAP and cidofovir were most potent in reducing plaque size. IC50 (SIZE) values were 0.4 microg/ml (1.7 microM), 0.9 microg/ml (2.7 microM) and 0.2 microg/ml (0.7 microM), respectively. Adefovir and foscarnet were intermediately potent, with an IC50 (SIZE) of 4 microg/ml (14.6 microM) and 7 microg/ml (36.4 microM), respectively. Acyclovir was least potent (IC50 (SIZE) of 15 microg/ml or 66.6 microM). The results demonstrate that the IC50 (SIZE) values were notably lower than the IC50 (NUMBER) values. The most remarkable effect was observed for cidofovir and ganciclovir. None of the products were toxic for CRFK cells at antiviral concentrations.

CONCLUSION

In conclusion, measuring reduction in plaque number and plaque size are two valuable and complementary means of assessing the efficacy of an antiviral drug. By using these parameters for six selected antiviral drugs, we found that ganciclovir, PMEDAP, and cidofovir are the most potent inhibitors of FHV-1 replication in CRFK cells. Therefore, they may be valuable candidates for the treatment of FHV-1 infection in cats.

摘要

背景

猫疱疹病毒1型(FHV-1)是猫呼吸道和眼部疾病的常见病因。特别是在尚未达到疫苗接种年龄但已失去母源免疫力的幼猫中,可能会发生严重疾病。因此,需要一种有效的抗病毒治疗方法。在本研究中,以斑块数量减少和斑块大小为参数,在克兰德尔-里斯猫肾(CRFK)细胞中比较了六种抗病毒药物,即阿昔洛韦、更昔洛韦、西多福韦、膦甲酸钠、阿德福韦和9-(2-膦酰甲氧基乙基)-2,6-二氨基嘌呤(PMEDAP)对FHV-1的疗效。

结果

更昔洛韦、PMEDAP和西多福韦减少斑块数量的能力最为显著。IC50(数量)值分别为3.2微克/毫升(12.5微摩尔)、4.8微克/毫升(14.3微摩尔)和6微克/毫升(21.5微摩尔)。阿德福韦和膦甲酸钠的效率中等,IC50(数量)分别为20微克/毫升(73.2微摩尔)和27微克/毫升(140.6微摩尔)。阿昔洛韦效率最低(IC50(数量)为56微克/毫升或248.7微摩尔)。与未处理的对照相比,所有抗病毒药物均能显著减小斑块大小。如在斑块数量减少方面观察到的,更昔洛韦、PMEDAP和西多福韦在减小斑块大小方面最有效。IC50(大小)值分别为0.4微克/毫升(1.7微摩尔)、0.9微克/毫升(2.7微摩尔)和0.2微克/毫升(0.7微摩尔)。阿德福韦和膦甲酸钠的效力中等,IC50(大小)分别为4微克/毫升(14.6微摩尔)和7微克/毫升(36.4微摩尔)。阿昔洛韦效力最低(IC50(大小)为15微克/毫升或66.6微摩尔)。结果表明,IC50(大小)值明显低于IC50(数量)值。西多福韦和更昔洛韦的效果最为显著。在抗病毒浓度下,所有产品对CRFK细胞均无毒性。

结论

总之,测量斑块数量减少和斑块大小是评估抗病毒药物疗效的两个有价值且互补的方法。通过将这些参数用于六种选定的抗病毒药物,我们发现更昔洛韦、PMEDAP和西多福韦是CRFK细胞中FHV-1复制的最有效抑制剂。因此,它们可能是治疗猫FHV-1感染的有价值候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bbb/1475582/7b199c7828e2/1746-6148-2-13-1.jpg

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