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High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
Published on: May 5, 2014
Inhibition of Hepatitis Delta Virus Genomic Ribozyme Self-Cleavage by Aminoglycosides
J.-S. Chia1, H.-L. Wu, H.-W. Wang
1Graduate Institutes of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Journal of Biomedical Science
|January 1, 1997
Summary
Aminoglycoside antibiotics inhibited hepatitis delta virus (HDV) ribozyme self-cleavage in vitro by interacting with its structure. However, these compounds did not suppress HDV activity in cell lines.
Area of Science:
- Molecular Biology
- Virology
- Biochemistry
Background:
- Hepatitis delta virus (HDV) RNA contains a ribozyme essential for its life cycle, dependent on a unique pseudoknot structure.
- Aminoglycosides are known to inhibit self-splicing of group I introns and aid in structure elucidation.
Purpose of the Study:
- To investigate the effects of aminoglycoside antibiotics on the HDV genomic ribozyme.
- To explore the potential of aminoglycosides in probing HDV ribozyme structure and reaction mechanisms.
Main Methods:
- Testing the inhibitory effects of various aminoglycosides (tobramycin, netromycin, neomycin, gentamicin) on HDV ribozyme self-cleavage in vitro.
- Assessing the influence of magnesium ion concentration on inhibition.
- Utilizing chemical modification mapping to identify RNA regions interacting with aminoglycosides.
- Evaluating the in vivo effects of aminoglycosides on HDV cleavage and replication in cell lines.
Main Results:
- Aminoglycosides effectively inhibited HDV genomic ribozyme self-cleavage in vitro at concentrations similar to those affecting group I introns.
- Inhibition was dependent on magnesium ion concentration.
- Chemical modification suggested tobramycin induced a conformational shift in the HDV ribozyme.
- No suppressive effects of aminoglycosides were observed in vivo on HDV cleavage and replication.
Conclusions:
- Aminoglycosides can inhibit HDV ribozyme self-cleavage in vitro, indicating interaction with its structure.
- The study provides initial insights into using aminoglycosides as structural probes for HDV ribozyme.
- Further research is needed to understand the discrepancy between in vitro and in vivo results and to explore therapeutic potential.
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