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PHA767491 对体外感染山羊疱疹病毒 1 的抗病毒活性。

Antiviral activity of PHA767491 on Caprine alphaherpesvirus 1 in vitro.

机构信息

Department of Veterinary Medicine, University of Bari, Valenzano, Bari, Italy.

Pharmacy, Farmacia San Giorgio, Roma, Italy.

出版信息

Res Vet Sci. 2019 Oct;126:113-117. doi: 10.1016/j.rvsc.2019.08.019. Epub 2019 Aug 12.

Abstract

Caprine alphaherpesvirus 1 (CpHV-1) induces genital lesions in its natural host similar to those caused by Human alphaherpesvirus 2 (HHV-2), commonly named herpes simplex virus 2 (HSV-2) in human patients. CpHV-1 infection in goats could represent a useful homologous animal model for the study of HSV-2 infection, chiefly for the assessment of antiviral drugs in in vivo studies. PHA767491 is a potent inhibitor of HSV-1 and HSV-2, being able to limit replication of HHVs both in vitro and in the mouse model. In the present study the antiviral efficacy of PHA767491 against CpHV-1 was evaluated in vitro in MDBK cells. PHA767491 inhibited significantly CpHV-1 replication in a dose-dependent fashion by up to 2.50 log10 TCID/50 μl and was able to decrease viral DNA by nearly 8 log10. These findings confirm that PHA767491 is highly effective not only against simplexviruses (HSV-1 and HSV-2), but also against the varicellovirus CpHV-1. Experiments will be necessary to assess whether PHA767491 is suitable for treatment of vaginal lesions in CpHV-1-goat model. This could provide hints for the therapy of genital alphaherpesvirus infections in humans.

摘要

山羊α疱疹病毒 1(CpHV-1)在其自然宿主中引起的生殖器病变与人类α疱疹病毒 2(HHV-2)引起的病变相似,在人类患者中通常称为单纯疱疹病毒 2(HSV-2)。山羊 CpHV-1 感染可能代表了一种用于研究 HSV-2 感染的有用同源动物模型,主要用于评估体内研究中的抗病毒药物。PHA767491 是一种有效的 HSV-1 和 HSV-2 抑制剂,能够在体外和小鼠模型中限制 HHVs 的复制。在本研究中,在 MDBK 细胞中评估了 PHA767491 对 CpHV-1 的体外抗病毒功效。PHA767491 以剂量依赖性方式显著抑制 CpHV-1 的复制,最高可达 2.50 log10 TCID/50 μl,并且能够使病毒 DNA 减少近 8 log10。这些发现证实 PHA767491 不仅对单纯疱疹病毒(HSV-1 和 HSV-2),而且对水痘病毒 CpHV-1 也非常有效。有必要进行实验来评估 PHA767491 是否适合治疗 CpHV-1-山羊模型中的阴道病变。这可能为人类生殖器疱疹病毒感染的治疗提供线索。

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