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High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
Published on: May 5, 2014
Human rhinovirus VPg uridylylation AlphaScreen for high-throughput screening
Rock Gingras1, Kevork Mekhssian, Craig Fenwick
11Biological Sciences Department, Boehringer Ingelheim (Canada) Ltd., Laval, QC, Canada.
Journal of Biomolecular Screening
|July 2, 2013
Summary
Researchers developed a high-throughput assay to find inhibitors of human rhinovirus (HRV) VPg uridylylation. This could lead to new treatments for HRV-induced respiratory conditions like asthma.
Area of Science:
- Virology
- Biochemistry
- Drug Discovery
Background:
- Picornaviruses require VPg uridylylation for genome replication.
- VPg-pUpU acts as the primer for viral genome replication.
- This process involves viral polymerase, RNA structures, and other viral proteins.
Purpose of the Study:
- To identify inhibitors of human rhinovirus (HRV) VPg uridylylation.
- To develop potential antiviral agents against HRV.
- To reduce HRV-induced lower airway inflammatory responses.
Main Methods:
- Reconstitution of the VPg uridylylation reaction.
- Development of an AlphaScreen assay for high-throughput screening.
- Validation using quantitative mass spectrometry.
Main Results:
- A functional AlphaScreen assay for VPg uridylylation was established.
- The assay utilizes a specific antiserum against uridylylated VPg.
- Assay results were confirmed by mass spectrometry.
Conclusions:
- The developed assay is suitable for high-throughput screening of potential antiviral compounds.
- Inhibiting VPg uridylylation is a viable strategy for antiviral drug development.
- This research may lead to therapies for asthma and COPD exacerbations caused by HRV.
