Vaccinia Virus Virulence Factor N1L is a Novel Promising Target for Antiviral Therapeutic Intervention
| Autor: | John C. Reed, Alexander E. Aleshin, Anton Cheltsov, C. Taylor Gilliland, Dayong Zhai, Eric Chi-Wang Yu, Andrey A. Bobkov, Mika Aoyagi, Robert C. Liddington, Ruben Abagyan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Models
Molecular Databases Factual Virulence Factors viruses Vaccinia virus Ligands Antiviral Agents Virulence factor Virus Article Cell Line chemistry.chemical_compound Structure-Activity Relationship Viral Proteins Phenols Proto-Oncogene Proteins Drug Discovery Stilbenes Humans Binding site Binding Sites Bcl-2-Like Protein 11 Calorimetry Differential Scanning Chemistry Membrane Proteins Virology Peptide Fragments Protein Structure Tertiary Viral replication Cell culture Docking (molecular) Resveratrol Mutation Molecular Medicine Thermodynamics Vaccinia Apoptosis Regulatory Proteins Ultracentrifugation Binding domain |
| Popis: | The 14 kDa homodimeric N1L protein is a potent vaccinia and variola (smallpox) virulence factor. It is not essential for viral replication, but it causes a strong attenuation of viral production in culture when deleted. The N1L protein is predicted to contain the BH3-like binding domain characteristic of Bcl-2 family proteins, and it is able to bind the BH3 peptides. Its overexpression has been reported to prevent infected cells from committing apoptosis. Therefore, interfering with the N1L apoptotic blockade may be a legitimate therapeutic strategy affecting the viral growth. By using in silico ligand docking and an array of in vitro assays, we have identified sub-micromolar (600 nM) N1L antagonists, belonging to the family of polyphenols. Their affinity is comparable to that of the BH3 peptides (70 nM ÷ 1000 nM). We have also identified the natural polyphenol resveratrol as a moderate N1L inhibitor. Finally, we show that our ligands efficiently inhibit growth of vaccinia virus. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|