INVITRO AND INVIVO PHLEBOVIRUS INHIBITION BY RIBAVIRIN
INVITRO AND INVIVO PHLEBOVIRUS INHIBITION BY RIBAVIRIN
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DOI：
10.1128/aac.32.3.331
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发表时间：
1988-03-01
影响因子：
4.9
通讯作者：
PIFAT, DY
中科院分区：
文献类型：
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作者：
SIDWELL, RW;HUFFMAN, JH;PIFAT, DY
利巴韦林(1-.beta.-D-ribofuranosyl-1，2，4-triazole-3-carboxamide)在体外对裂谷热和沙蝇热病毒相关的Punta Toro病毒Adames株和Balliet株有明显的抑制作用。通过抑制两株病毒对LLC-MK2细胞的细胞病变效应，50%有效剂量为4~10微克/毫升，病毒等级为1.3。为评价利巴韦林的体内抗病毒作用，建立了PTV感染小鼠Adams株。这种药物是皮下注射的(S.C.)从病毒接种前4h、病毒接种后24h或病毒接种后36h开始，每天2次，连续5~7d，可增加小鼠存活率，减少肝黄疸，降低血清谷草转氨酶和血清谷丙转氨酶，并抑制感染小鼠血清和肝脏中的感染性病毒。最小有效剂量为4.7 mg/kg/d，最大耐受量为75 mg/kg/d。在病毒前4h、病毒后4h或病毒后24h开始接种相同的治疗程序时，口服利巴韦林的剂量低至6.3 mg/kg/d。单人S.C.病毒接种后4~48h给予175~700 mg/kg的利巴韦林治疗同样有效。皮下注射利巴韦林未见效果。对脑内感染PTV Balliet株的小鼠，即使在病毒暴露前36小时开始治疗也是如此。
Ribavirin (1-.beta.-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) was markedly inhibitory in vitro to Adames and Balliet strains of Punta Toro virus (PTV), a Phlebovirus related to Rift Valley fever and sandfly fever viruses. By using inhibition of viral cytopathic effect in LLC-MK2 cells with both virus strains, the 50% effective dose was 4 to 10 .mu.g/ml and the virus rating was 1.3. The Adames strain of PTV infection in mice was established for evaluation of the in vivo antiviral efficacy of ribavirin. The drug was administered subcutaneously (s.c.) twice daily for 5 to 7 days beginning 4 h pre-virus inoculation, 24 h post-virus inoculation, or 36 h post-virus inoculation, with increased survivors, reduced hepatic icterus, reduction of serum glutamic oxalic acid transaminase and serum glutamic pyruvic acid transaminase, and inhibition of infectious virus from sera and livers of infected mice. The minimum effective dose was 4.7 mg/kg per day, with a maximum tolerated dose of 75 mg/kg per day. When the same treatment schedule beginning 4 h pre-virus inoculation, 4 h post-virus inoculation, or 24 h post-virus inoculation was used, orally administered ribavirin was effective at doses as low as 6.3 mg/kg per day. Single s.c. ribavirin treatments at doses of 175 to 700 mg/kg administered from 4 to 48 h post-virus inoculation were also effective. No effect was seen when ribavirin was administered s.c. to mice infected intracerebrally with the PTV strain Balliet, even though treatment was begun 36 h before virus exposure.