Broad-Spectrum Antiviral Entry Inhibition by Interfacially Active Peptides

Area of Science:

• Biochemistry
• Virology
• Drug Discovery

Background:

• Broad-spectrum antiviral peptides are needed due to the limitations of current antiviral drugs.
• Interfacial activity, the ability to interact with lipid bilayer membranes, is a proposed mechanism for broad-spectrum antiviral activity.

Purpose of the Study:

• To test the hypothesis that interfacial activity correlates with broad-spectrum antiviral activity.
• To evaluate the antiviral efficacy of membrane-disrupting peptides against diverse enveloped viruses.

Main Methods:

• Selected families of peptides with membrane-disrupting properties but no known antiviral activity were tested.
• Peptides were evaluated for their ability to inhibit Lassa pseudovirus, influenza virus, dengue virus type 2, herpes simplex virus 1, and human adenovirus 5.

Main Results:

• Interfacially active peptides potently inhibited all tested enveloped viruses at low, non-toxic concentrations.
• These peptides act by directly interacting with virions, destabilizing the viral envelope, and promoting aggregation or fusion.

Conclusions:

• Interfacial activity is a strong correlate of broad-spectrum antiviral activity.
• These findings suggest that interfacially active peptides can be exploited to design novel broad-spectrum antiviral therapeutics.