AI Article Synopsis
- Norovirus (NV) is a leading cause of gastroenteritis worldwide, creating a demand for effective antiviral treatments.
- A focus on the RNA-dependent-RNA-polymerase (RdRp) protein has led to the identification of the compound PPNDS, which demonstrates significant inhibitory activity against murine NV-RdRp.
- The crystal structure of the murine NV-RdRp/PPNDS complex reveals that PPNDS binds in a way that blocks RNA exit, mimicking the interaction of stacked nucleotide bases in the RdRp/ssRNA complex.
Article Abstract
Norovirus (NV) is a major cause of gastroenteritis worldwide. Antivirals against such important pathogens are on demand. Among the viral proteins that orchestrate viral replication, RNA-dependent-RNA-polymerase (RdRp) is a promising drug development target. From an in silico-docking search focused on the RdRp active site, we selected the compound PPNDS, which showed low micromolar IC50vs. murine NV-RdRp in vitro. We report the crystal structure of the murine NV-RdRp/PPNDS complex showing that two molecules of the inhibitor bind in antiparallel stacking interaction, properly oriented to block exit of the newly synthesized RNA. Such inhibitor-binding mode mimics two stacked nucleotide-bases of the RdRp/ssRNA complex.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.febslet.2014.03.021 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!