Romero Marta R, Serrano Maria A, Vallejo Marta, Efferth Thomas, Alvarez Marcelino, Marin Jose J G
Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), University of Salamanca, Salamanca, Spain.
Planta Med. 2006 Oct;72(13):1169-74. doi: 10.1055/s-2006-947198. Epub 2006 Aug 10.
The antiviral activity versus flaviviruses of artemisinin, a safe drug obtained from Artemisia annua and commonly used to treat malaria, has been investigated using as an IN VITRO model bovine epithelial cells from embryonic trachea (EBTr) infected with the cytopathic strain Oregon C24V, of bovine viral diarrhoea virus (BVDV), which is a member of the Flaviviridae family. Antiviral activity was estimated by the degree of protection against the cytopathic effect of BVDV on host cells and by the reduction in BVDV-RNA release to the culture medium. To induce an intermediate cytopathic effect in non-treated cells, EBTr cells were first exposed to BVDV for 48 h and then incubated with virus-free medium for 72 h. Ribavirin and artemisinin (up to 100 microM) induced no toxicity in host cells, whereas a slight degree of toxicity was observed for IFN-alpha at concentrations above 10 U/mL up to 100 U/mL. Treatment of infected cells with IFN-alpha, ribavirin and artemisinin markedly reduced BVDV-induced cell death. A combination of these drugs resulted in an additive protective effect. These drugs induced a significant reduction in the production/release of BVDV virions by infected EBTr cells; there was also an additive effect when combinations of them were assayed. These results suggest a potential usefulness of artemisinin in combination with current pharmacological therapy for the treatment of human and veterinary infections by flaviviruses.
青蒿素是从青蒿中提取的一种安全药物,常用于治疗疟疾,其对黄病毒的抗病毒活性已通过体外模型进行研究。该模型使用感染了牛病毒性腹泻病毒(BVDV)细胞病变株俄勒冈C24V的胚胎气管牛上皮细胞(EBTr),BVDV是黄病毒科的成员。通过对宿主细胞抵抗BVDV细胞病变效应的保护程度以及BVDV-RNA释放到培养基中的减少程度来评估抗病毒活性。为了在未处理的细胞中诱导中等程度的细胞病变效应,首先将EBTr细胞暴露于BVDV 48小时,然后在无病毒培养基中孵育72小时。利巴韦林和青蒿素(高达100微摩尔)对宿主细胞无毒性,而在浓度高于10国际单位/毫升至100国际单位/毫升时,观察到α干扰素存在轻微毒性。用α干扰素、利巴韦林和青蒿素处理感染细胞可显著降低BVDV诱导的细胞死亡。这些药物联合使用产生了相加的保护作用。这些药物显著降低了感染的EBTr细胞产生/释放BVDV病毒粒子的量;对它们的组合进行检测时也存在相加效应。这些结果表明青蒿素与当前药物疗法联合使用在治疗人和动物黄病毒感染方面具有潜在的应用价值。