Flaviviruses, such as Dengue (DENV) and Zika (ZIKV) viruses, represent a severe health burden. There are currently no FDA-approved treatments, and vaccines against most flaviviruses are still lacking. We have developed several flexible analogues (“fleximers”) of the FDA-approved nucleoside Acyclovir that exhibit activity against various RNA viruses, demonstrating their broad-spectrum potential. The current study reports activity against DENV and YFV, particularly for compound 1. Studies to elucidate the mechanism of action suggest the flex-analogue triphosphates, especially 1-TP, inhibit DENV and ZIKV methyltransferases. The results of these studies are reported herein.

黄病毒，例如登革热 (DENV) 和寨卡 (ZIKV) 病毒，带来了严重的健康负担。目前还没有 FDA 批准的治疗方法，并且仍然缺乏针对大多数黄病毒的疫苗。我们开发了 FDA 批准的核苷阿昔洛韦的几种灵活类似物（“fleximers”），它们表现出对抗各种 RNA 病毒的活性，展示了其广谱潜力。目前的研究报告了针对 DENV 和 YFV 的活性，特别是化合物1。阐明作用机制的研究表明，柔性类似物三磷酸盐，尤其是1-TP，可抑制 DENV 和 ZIKV 甲基转移酶。这些研究的结果在此报告。