Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
Center of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.
Sci Rep. 2023 Mar 25;13(1):4891. doi: 10.1038/s41598-023-32049-x.
Dengue and Zika viruses are mosquito-borne flaviviruses burdening millions every year with hemorrhagic fever and neurological symptoms. Baicalein was previously reported as a potential anti-flaviviral candidate and halogenation of flavones and flavanones potentiated their antiviral efficacies. Here, we reported that a chemically modified 8-bromobaicalein effectively inhibited all dengue serotypes and Zika viruses at 0.66-0.88 micromolar in cell-based system. The compound bound to dengue serotype 2 conserved pocket and inhibited the dengue RdRp activity with 6.93 fold more than the original baicalein. Moreover, the compound was mildly toxic against infant and adult C57BL/6 mice despite administering continuously for 7 days. Therefore, the 8-bromobaicalein should be investigated further in pharmacokinetics and efficacy in an animal model.
登革热和寨卡病毒是通过蚊子传播的黄病毒，每年都会使数百万人患上出血热和神经系统症状。黄芩素先前被报道为一种有潜力的抗黄病毒候选药物，而黄酮和黄烷酮的卤化增强了它们的抗病毒功效。在这里，我们报告了一种化学修饰的 8-溴黄芩素在细胞水平上以 0.66-0.88 微摩尔的浓度有效抑制所有登革热血清型和寨卡病毒。该化合物与登革热血清型 2 的保守口袋结合，并以比原始黄芩素高 6.93 倍的抑制登革热 RdRp 活性。此外，该化合物对婴儿和成年 C57BL/6 小鼠的毒性较低，尽管连续给药 7 天。因此，8-溴黄芩素应该在药代动力学和动物模型中的疗效方面进行进一步研究。
