Evaluation of Sofosbuvir (β-D-2'-deoxy-2'-α-fluoro-2'-β-C-methyluridine) as an inhibitor of Dengue virus replication^.

ABSTRACT: We evaluated Sofosbuvir (SOF), the anti-hepatitis C virus prodrug of β-d-2'-deoxy-2'-α-fluoro-2'-β-C-methyluridine-5'-monophosphate, for potential inhibitory activity against DENV replication. Both cell-based and biochemical assays, based on use of purified DENV full-length NS5 enzyme, were studied. Cytopathic effect protection and virus yield reduction assays confirmed that SOF possessed anti-DENV activity in cell culture with a 50% effective concentration (EC₅₀) of 4.9 µM and 1.4 µM respectively. Real-time RT-PCR verified that SOF inhibits generation of viral RNA with an EC₅₀ of 9.9 µM. Purified DENV NS5 incorporated the active triphosphate form (SOF-TP) into nascent RNA, causing chain-termination. Relative to the natural UTP, the incorporation efficiency of SOF-TP

SUBMITTER: Xu HT 

PROVIDER: S-EPMC5524696 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature