PDF(Pubmed)
Abstract：
Chikungunya virus is a re-emerging arbovirus that has caused epidemic outbreaks in recent decades. Patients in older age groups with high viral load and severe immunologic response during acute infection are likely to develop chronic arthritis and severe joint pain. Currently, no antiviral drug is available. Previous studies suggested that a flavone derivative, 8-bromobaicalein, was a potential dengue and Zika replication inhibitor in a cell-based system targeting flaviviral polymerase. Here we characterized that 8-bromobaicalein inhibited chikungunya virus replication with EC50 of 0.49 ± 0.11 µM in Vero cells. The molecular target predicted at viral nsP1 methyltransferase using molecular binding and fragment molecular orbital calculation. Additionally, oral administration of 250 mg/kg twice daily treatment alleviated chikungunya-induced musculoskeletal inflammation and reduced viral load in healthy adult mice. Pharmacokinetic analysis indicated that the 250 mg/kg administration maintained the compound level above EC99.9 for 12 h. Therefore, 8-bromobaicalein should be a potential candidate for further development as a pan-arboviral drug.
摘要：
基孔肯雅病毒是一种重新出现的虫媒病毒，近几十年来引起了流行病的爆发。在急性感染期间，高病毒载量和严重免疫反应的老年患者可能会发展为慢性关节炎和严重的关节痛。目前,没有抗病毒药物可用。以前的研究表明，黄酮衍生物，8-bromobaicalein,是靶向黄病毒聚合酶的基于细胞的系统中潜在的登革热和寨卡病毒复制抑制剂。在这里，我们表征了8-溴黄芩素在Vero细胞中以0.49±0.11µM的EC50抑制基孔肯雅病毒复制。使用分子结合和片段分子轨道计算预测病毒nsP1甲基转移酶的分子靶标。此外,口服250mg/kg每日两次治疗可减轻基孔肯雅诱导的肌肉骨骼炎症，并降低健康成年小鼠的病毒载量。药代动力学分析表明,250mg/kg给药使化合物水平维持在EC99.9以上12小时。8-溴黄芩素应该是进一步开发为泛虫媒病毒药物的潜在候选者。
