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对持续感染牛病毒性腹泻病毒的犊牛进行抗病毒治疗。

Antiviral treatment of calves persistently infected with bovine viral diarrhoea virus.

作者信息

Newcomer Benjamin W, Marley M Shonda, Galik Patricia K, Walz Paul H, Zhang Yijing, Riddell Kay P, Dykstra Christine C, Boykin David W, Kumar Arvind, Cruz-Espindola Crisanta, Boothe Dawn M, Joiner Kellye S, Givens M Daniel

机构信息

Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL, USA.

出版信息

Antivir Chem Chemother. 2012 Jan 17;22(4):171-9. doi: 10.3851/IMP1903.

Abstract

BACKGROUND

Animals persistently infected (PI) with bovine viral diarrhoea virus (BVDV) are a key source of viral propagation within and among herds. Currently, no specific therapy exists to treat PI animals. The purpose of this research was to initiate evaluation of the pharmacokinetic and safety data of a novel antiviral agent in BVDV-free calves and to assess the antiviral efficacy of the same agent in PI calves.

METHODS

One BVDV-free calf was treated with 2-(2-benzimidazolyl)-5-[4-(2-imidazolino)phenyl]furan dihydrochloride (DB772) once at a dose of 1.6 mg/kg intravenously and one BVDV-free calf was treated three times a day for 6 days at 9.5 mg/kg intravenously. Subsequently, four PI calves were treated intravenously with 12 mg/kg DB772 three times a day for 6 days and two PI control calves were treated with an equivalent volume of diluent only.

RESULTS

Prior to antiviral treatment, the virus isolated from each calf was susceptible to DB772 in vitro. The antiviral treatment effectively inhibited virus for 14 days in one calf and at least 3 days in three calves. Subsequent virus isolated from the three calves was resistant to DB772 in vitro. No adverse effects of DB772 administration were detected.

CONCLUSIONS

Results demonstrate that DB772 administration is safe and exhibits antiviral properties in PI calves while facilitating the rapid development of viral resistance to this novel therapeutic agent.

摘要

背景

持续感染牛病毒性腹泻病毒(BVDV)的动物是牛群内部及牛群之间病毒传播的关键来源。目前,尚无治疗持续性感染动物的特效疗法。本研究的目的是开始评估一种新型抗病毒药物在无BVDV犊牛中的药代动力学和安全性数据,并评估该药物在持续性感染犊牛中的抗病毒疗效。

方法

一头无BVDV犊牛静脉注射一次2-(2-苯并咪唑基)-5-[4-(2-咪唑啉基)苯基]呋喃二盐酸盐(DB772),剂量为1.6mg/kg;另一头无BVDV犊牛每天静脉注射3次,持续6天,剂量为9.5mg/kg。随后,4头持续性感染犊牛每天静脉注射3次,剂量为12mg/kg DB772,持续6天;2头持续性感染对照犊牛仅用等量稀释剂治疗。

结果

在进行抗病毒治疗前,从每头犊牛分离出的病毒在体外对DB772敏感。抗病毒治疗在1头犊牛中有效抑制病毒达14天,在3头犊牛中至少抑制3天。随后从这3头犊牛分离出的病毒在体外对DB772耐药。未检测到DB772给药的不良反应。

结论

结果表明,给予DB772是安全的,在持续性感染犊牛中具有抗病毒特性,同时促进了病毒对这种新型治疗药物的快速耐药性发展。

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