Drug Discovery & Disease Research Laboratory, Shionogi & Co., Ltd., Osaka, Japan; Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
Drug Discovery & Disease Research Laboratory, Shionogi & Co., Ltd., Osaka, Japan.
Antiviral Res. 2018 Jul;155:60-66. doi: 10.1016/j.antiviral.2018.05.003. Epub 2018 May 11.
Dengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic fever/dengue shock syndrome. At present, no antiviral drugs are available for treatment DENV infections. In this study, a screening system based on a DENV-infected cell-based assay identified a novel anti-DENV agent with a benzimidazole skeleton, named Compound-B, which demonstrated antiviral activity specific to four DENV serotypes (EC: 1.32-4.12 μM). Analysis of a single amino acid substitution of Compound-B-resistant DENV2 revealed that mutation C87S in the non-structural protein 4A (NS4A) contributes to resistance to Compound-B.
登革热病毒（DENV）是登革热和登革出血热/登革休克综合征的病原体。目前，尚无抗病毒药物可用于治疗 DENV 感染。在本研究中，一种基于感染登革热病毒的细胞检测的筛选系统发现了一种新型苯并咪唑骨架的抗 DENV 药物，命名为化合物-B，对四种 DENV 血清型具有抗病毒活性（EC：1.32-4.12 μM）。对化合物-B 耐药的 DENV2 的单个氨基酸取代分析表明，非结构蛋白 4A（NS4A）中的 C87S 突变有助于对化合物-B 的耐药性。
