Substituted benzimidazoles: antiviral activity and synthesis of nucleosides
ARKIVOC
Authors: Budow, Simone; Kozlowska, Mariola; Gorska, Agata; Kazimierczuk, Zygmunt; Eickmeier, Henning; La Colla, Paolo; Gosselin, Gilles; Seela, Frank
Abstract
The antiviral activity of a series of benzimidazole derivatives and substituted benzimidazole beta-L- and beta-D-2'-deoxyribonucleosides against selected RNA and DNA viruses including HIV-1, BVDV, YFV, DENV-2, WNV, HBV, HCV and human RSV was evaluated. In addition, the synthesis of several benzimidazole beta-L-2'-deoxyribonucleosides (1-4) and 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl nucleoside 5 is described. The stereoselective glycosylation of the anions of the functionalized benzimidazoles 6a, 12a and 28 with 3,5-di-O-(4-methylbenzoyl)-2-deoxy-alpha-L-erythro-pentofuranosyl chloride (29) furnished beta-L-2'-deoxyribonucleosides 1-4 while the glycosylation of the anion of 2-bromobenzimidazole (12a) with 3,5-di-O-benzoyl-2-deoxy-2-fluoro-alpha-D-arabinofuranosyl bromide 34 gave the 2'-deoxy-2-fluoro-beta-D-arabinofuranosyl nucleoside 5. Moreover, the crystal structure of the benzoylated 2-bromobenzimidazole 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl nucleoside 35 is reported.
Yellow Fever Virus: Knowledge Gaps Impeding the Fight Against an Old Foe
TRENDS IN MICROBIOLOGY
Authors: Douam, Florian; Ploss, Alexander
Abstract
Yellow fever (YF) was one of the most dangerous infectious diseases of the 18th and 19th centuries, resulting in mass casualties in Africa and the Americas. The etiologic agent is yellow fever virus (YFV), and its live-attenuated form, YFV-17D, remains one of the most potent vaccines ever developed. During the first half of the 20th century, vaccination combined with mosquito control eradicated YFV transmission in urban areas. However, the recent 2016-2018 outbreaks in areas with historically low or no YFV activity have raised serious concerns for an estimated 400-500 million unvaccinated people who now live in at-risk areas. Once a forgotten disease, we highlight here that YF still represents a very real threat to human health and economies. As many gaps remain in our understanding of how YFV interacts with the human host and causes disease, there is an urgent need to address these knowledge gaps and propel YFV research forward.