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Early Viral Entry Assays for the Identification and Evaluation of Antiviral Compounds
Published on: October 29, 2015
Human rhinovirus 14 complexed with fragments of active antiviral compounds
J K Bibler-Muckelbauer1, M J Kremer, M G Rossmann
1Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907-1392.
Virology
|July 1, 1994
Summary
Short antiviral WIN compounds bind to human rhinovirus 14, mimicking cellular cofactors. These compounds stabilize the virus capsid but do not inhibit attachment, offering insights into picornavirus drug development.
Area of Science:
- Structural biology
- Virology
- Drug discovery
Background:
- Human rhinovirus 14 (HRV14) is a significant human pathogen.
- Antiviral WIN compounds target a hydrophobic pocket in the viral protein VP1.
- Understanding drug-virus interactions is crucial for developing effective antiviral therapies.
Purpose of the Study:
- To investigate the binding of short WIN compound fragments to HRV14.
- To determine the effect of these compounds on viral capsid stability and conformation.
- To elucidate the mechanism of action for potential antiviral agents.
Main Methods:
- High-concentration crystallographic studies of HRV14 soaked with WIN compound fragments.
- Thermostabilization assays to assess capsid stability.
- Analysis of structural changes induced by compound binding.
Main Results:
- Short WIN compounds bind to the hydrophobic WIN pocket in VP1.
- Two specific compounds induced conformational changes similar to longer WIN compounds.
- These compounds conferred a degree of thermostability to the HRV14 capsid.
- Binding sites for dimethyl sulfoxide (DMSO) solvent were also identified.
Conclusions:
- Short WIN compounds mimic cellular cofactors by binding to the VP1 hydrophobic pocket.
- They induce conformational changes and provide virion stabilization.
- These compounds are unlikely to inhibit viral attachment, suggesting a different mechanism of action.
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