Glyoxal Caging of Nucleoside Antivirals toward Self-Activating, Extended-Release Prodrugs.

ABSTRACT: Nucleoside antivirals are a leading class of compounds prescribed as a first-line treatment for viral infections. However, inherent limitations such as low solubility and circulation lifetime can necessitate multi-intraday dosing. Here, we deploy the 1,2-dialdehyde glyoxal to generate antiviral nucleoside prodrugs with enhanced pharmacokinetic properties and extended-release activity to combat poor patient adherence. The near-quantitative reaction of glyoxal with acyclovir (ACV) drastically improves ACV solubility and enables subsequent drug release with a half-life of 1.9 h under physiological conditions. Further, glyoxal caging thermoreversibly disrupts ACV activity against HIV-1 reverse transcription in vitro and HSV-1 pathology in cellulo. Finally, the amenability of a pa

SUBMITTER: Karloff DB 

PROVIDER: S-EPMC11867213 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature