Related Experiment Video
Updated: Oct 2, 2025
High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication
Published on: October 30, 2021
High Throughput Screening Targeting the Dengue NS3-NS5 Interface Identifies Antivirals against Dengue, Zika and West
Sundy N Y Yang1, Belinda Maher1, Chunxiao Wang1
1Nuclear Signalling Laboratory, Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Monash, VIC 3800, Australia.
Abstract:
Dengue virus (DENV) threatens almost 70% of the world's population, with no effective therapeutic currently available and controversy surrounding the one approved vaccine. A key factor in dengue viral replication is the interaction between DENV nonstructural proteins (NS) 5 and 3 (NS3) in the infected cell. Here, we perform a proof-of-principle high-throughput screen to identify compounds targeting the NS5-NS3 binding interface. We use a range of approaches to show for the first time that two small molecules-repurposed drugs I-OMe tyrphostin AG538 (I-OMe-AG238) and suramin hexasodium (SHS)-inhibit NS5-NS3 binding at low μM concentration through direct binding to NS5 that impacts thermostability. Importantly, both have strong antiviral activity at low μM concentrations against not only DENV-2, but also Zika virus (ZIKV) and West Nile virus (WNV). This work highlights the NS5-NS3 binding interface as a viable target for the development of anti-flaviviral therapeutics.
