Bioorganic & medicinal chemistry · 2025
Exploration of 4'-fluoro fleximer nucleoside analogues as potential broad-spectrum antiviral agents.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Davis Kyle A, Smith Jason K, Smith Jessica L, Amare Meareg, Diefenbacher Meghan V, Halfmann Peter, Sheahan Timothy P, Hirsch Alec J, Seley-Radtke Katherine L
Аннотация
A series of 4'-fluoro fleximer nucleoside analogues in addition to their corresponding prodrugs were designed, synthesized, and evaluated for their antiviral potential. The impetus for this series was based on the success of other 4'-modified nucleoside antiviral drugs such as adafosbuvir and balapiravir. One analogue, KAD-008, exhibited potent, low single-digit micromolar activity against DENV-2. Another analogue, KAD-025, had broad-spectrum antiviral activity across several viral families including flaviviruses, filoviruses, and coronaviruses. All of the analogues tested showed no toxicity up to 100 µM. Additional studies are underway to elucidate the mechanism of action for these compounds and to synthesize additional 4'-modified fleximer nucleoside analogues with different 4'-modifications to compare their antiviral activities.