PPNDS inhibits murine Norovirus RNA-dependent RNA-polymerase mimicking two RNA stacking bases
Articolo
Data di Pubblicazione:
2014
Citazione:
PPNDS inhibits murine Norovirus RNA-dependent RNA-polymerase mimicking two RNA stacking bases / R. Croci, D. Tarantino, M. Milani, M. Pezzullo, J. Rohayem, M. Bolognesi, E. Mastrangelo. - In: FEBS LETTERS. - ISSN 0014-5793. - 588:9(2014 May), pp. 1720-1725. [10.1016/j.febslet.2014.03.021]
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 IC50 vs. 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. © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Antiviral discovery ; In silico-docking ; Norovirus ; PPNDS ; RNA-dependent-RNA-polymerase ; X-ray crystallography ; Animals ; Antiviral Agents ; Catalytic Domain ; Crystallography, X-Ray ; Mice ; Models, Molecular; Norovirus ; Protein Binding ; Protein Structure, Secondary ; Pyridoxal Phosphate ; RNA Replicase ; Sulfonic Acid s; Viral Proteins ; Biochemistry ; Biophysics ; Cell Biology ; Genetics ; Molecular Biology ; Structural Biology
Elenco autori:
R. Croci, D. Tarantino, M. Milani, M. Pezzullo, J. Rohayem, M. Bolognesi, E. Mastrangelo
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