Laboratory of Clinical Virology, Zoonotic Infectious Diseases Unit, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium.
Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.
Front Cell Infect Microbiol. 2021 Mar 15;11:580532. doi: 10.3389/fcimb.2021.580532. eCollection 2021.
We investigated whether chloroquine can prevent hantavirus infection and disease and , using the Hantaan virus newborn C57BL/6 mice model and the Syrian hamster model for Andes virus. antiviral experiments were performed using Vero E6 cells, and Old World and New World hantavirus species. Hantavirus RNA was detected using quantitative RT-PCR. For all hantavirus species tested, results indicate that the IC of chloroquine (mean 10.2 ± 1.43 μM) is significantly lower than the CC (mean 260 ± 2.52 μM) yielding an overall selectivity index of 25.5. We also investigated the potential of chloroquine to prevent death in newborn mice after Hantaan virus infection and its antiviral effect in the hantavirus Syrian hamster model. For this purpose, C57Bl/6 mother mice were treated subcutaneously with daily doses of chloroquine. Subsequently, 1-day-old suckling mice were inoculated intracerebrally with 5 x 10 Hantaan virus particles. In litters of untreated mothers, none of the pups survived challenge. The highest survival rate (72.7% of pups) was found when mother mice were administered a concentration of 10 mg/kg chloroquine. Survival rates declined in a dose-dependent manner, with 47.6% survival when treated with 5 mg/kg chloroquine, and 4.2% when treated with 1 mg/kg chloroquine. Assessing the antiviral therapeutic and prophylactic effect of chloroquine in the Syrian hamster model was done using two different administration routes (intraperitoneally and subcutaneously using an osmotic pump system). Evaluating the prophylactic effect, a delay in onset of disease was noted and for the osmotic pump, 60% survival was observed. Our results show that chloroquine can be highly effective against Hantaan virus infection in newborn mice and against Andes virus in Syrian hamsters.
我们研究了氯喹是否可以预防汉坦病毒感染和疾病,并使用汉坦病毒新生 C57BL/6 小鼠模型和安第斯病毒的叙利亚仓鼠模型进行了抗病毒实验。使用 Vero E6 细胞和旧世界和新世界汉坦病毒物种进行抗病毒实验。使用定量 RT-PCR 检测汉坦病毒 RNA。对于所有测试的汉坦病毒物种,结果表明氯喹的 IC(平均值 10.2±1.43μM)明显低于 CC(平均值 260±2.52μM),产生总体选择性指数为 25.5。我们还研究了氯喹预防新生小鼠感染汉坦病毒后死亡的潜力及其在汉坦病毒叙利亚仓鼠模型中的抗病毒作用。为此,C57Bl/6 母鼠每天皮下给予氯喹治疗。随后,用 5×10 个汉坦病毒颗粒脑内接种 1 日龄乳鼠。在未处理的母鼠的幼鼠中,没有一个幼鼠存活下来。当母鼠给予 10mg/kg 氯喹的浓度时,发现最高的存活率(72.7%的幼鼠)。当用 5mg/kg 氯喹治疗时,存活率下降到 47.6%,当用 1mg/kg 氯喹治疗时,存活率下降到 4.2%。通过两种不同的给药途径(腹膜内和皮下使用渗透泵系统)评估氯喹在叙利亚仓鼠模型中的抗病毒治疗和预防效果。评估预防效果时,注意到疾病发作的延迟,对于渗透泵,观察到 60%的存活率。我们的结果表明,氯喹对新生小鼠的汉坦病毒感染和叙利亚仓鼠的安第斯病毒非常有效。