CC BY-NC-ND 4.0Rähse, NickLapsien, MarcoGohlke, Holger2025-09-262025-09-262025https://researchdata.hhu.de/handle/entry/193https://doi.org/10.25838/d5p-82Viral infections pose significant challenge due to limited availability and efficacy of treatments. Current therapies primarily inhibit viral replication, but are often virus-specific and may lead to drug resistance. Sulfated glycosaminoglycans (GAGs) emerged as promising candidates for antiviral therapy, preventing viral binding to host cells and inhibiting cell entry, offering a novel therapeutic strategy targeting broad range of viruses, addressing the limitations of existing antiviral drugs. Here, we demonstrate highly-sulfated GAGs are able to limit infectivity of different pathogenic and non-pathogenic Arenaviruses. In an in vivo model setting, dextran sulfate administered during the acute phase of LCMV infection reduced viral load in organs and decreased liver pathology, which was associated with improved effector T cell functions. In turn, exposure of LCMV towards dextran sulfate at the beginning of infection caused limited immune activation, resulting in reduced T cell immunity, prolonged infection and increased immunopathology. These findings indicate the potential use of GAGs against Arenavirus infections and highlight that timing of therapeutic regimens might be critical for clinical efficacy.https://creativecommons.org/licenses/by-nc-nd/4.0/