Summary
Professor Michael Jung's group at UCLA has developed a novel class of compounds with broad spectrum antiviral activity toward enveloped viruses.
Background
Advances in antiviral treatments have allowed clinicians to control and manage many life-threatening viral infections. Most notably, these therapies have focused on the treatment of HIV, herpes viruses, hepatitis B and C, and influenza A and B. Current drug treatments are designed under what is known as the "one bug one drug" paradigm, where antiviral action is targeted to virus-specific proteins necessary for survival and replication. While the high specificity can be very effective, these virus-specific treatments suffer from long development times and eventual drug resistance, underlying a need for the development of broad spectrum antivirals that target pathways common to many types or classes of virus.
Innovation
The Jung group has identified a novel class of compounds known as a oxazolidine-2,4-dithiones with broad spectrum antiviral properties. These compounds can be readily synthesized from commercially available precursors and reagents, and have demonstrated strong antiviral activity at low nanomolar concentrations without host cytotoxicity. Unlike virus specific treatments, these novel antiviral compounds target the lipid membrane of enveloped viruses (e.g. herpes, influenza, HIV, etc.). Once localized to the lipid membrane, these compounds can be photochemically activated to disrupt the viral envelope to render the virus non-infectious. Strong antiviral activity has been demonstrated in vitro in cells infected with HIV and Newcastle disease, and in vivo in mice infected with Rift Valley Virus, highlighting the broad spectrum effect toward multiple enveloped viruses.
Applications
- These compounds can be developed into oral or topical antiviral therapeutics against enveloped viral infections such as HIV or herpes.
- These compounds can be used as a differential diagnostic to determine virus type to guide treatment.
- These compounds can be used as sterilizing agents or decontaminants for blood or cleaning products.
Advantages
- These antiviral compounds have demonstrated broad spectrum activity toward a variety of unrelated enveloped viruses.
- These compounds are potentially immune to viral resistance given the mechanism of action against the viral membrane and not specific proteins.
- These compounds are photosensitive to visible light, allowing for non-cytotoxic concentrations to be used while avoiding the hazards of UV exposure.
- These compounds are readily synthesized from available commercial reagents.
State Of Development
Two antiviral compounds have been synthesized based on improvements from previous antiviral work. These novel antiviral compounds have demonstrated the ability to inhibit viral infection both in vitro and in vivo.