1. Photodynamic Inactivation of Herpes Simplex Viruses
- Author
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Mackenzie Thornbury, Craig McCormick, Brett A. Duguay, Susan Monro, Colin G. Cameron, A.L. Monjo, Marc Hetu, Eric S. Pringle, Sherri A. McFarland, and Danika Knight
- Subjects
0301 basic medicine ,Foscarnet ,natural product ,Herpesvirus 2, Human ,viruses ,lcsh:QR1-502 ,Herpesvirus 1, Human ,medicine.disease_cause ,Plant Roots ,lcsh:Microbiology ,Chlorocebus aethiops ,Photosensitizer ,Virus quantification ,0303 health sciences ,Photosensitizing Agents ,biology ,Chemistry ,HSV-2 ,Antimicrobial ,HSV-1 ,antiviral ,virology ,3. Good health ,Infectious Diseases ,Capsid ,Vesicular stomatitis virus ,medicine.drug ,030103 biophysics ,Antiviral Agents ,Article ,photodynamic inactivation ,03 medical and health sciences ,Antigen ,Virology ,Fallopia japonica ,medicine ,Animals ,Humans ,Vero Cells ,030304 developmental biology ,Plant Extracts ,030306 microbiology ,plaque assay ,Herpes Simplex ,biology.organism_classification ,030104 developmental biology ,HEK293 Cells ,Herpes simplex virus ,Photochemotherapy ,HeLa Cells - Abstract
Herpes simplex virus (HSV) infections can be treated with direct acting antivirals like acyclovir and foscarnet, but long-term use can lead to drug resistance, which motivates research into broadly-acting antivirals that can provide a greater genetic barrier to resistance. Photodynamic inactivation (PDI) employs a photosensitizer, light, and oxygen to create a local burst of reactive oxygen species that inactivate microorganisms. The botanical plant extract OrthoquinTM is a powerful photosensitizer with antimicrobial properties. Here we report that Orthoquin also has antiviral properties. Photoactivated Orthoquin inhibited herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) infection of target cells in a dose-dependent manner across a broad range of sub-cytotoxic concentrations. HSV inactivation required direct contact between Orthoquin and the inoculum, whereas pre-treatment of target cells had no effect. Orthoquin did not cause appreciable damage to viral capsids or premature release of viral genomes, as measured by qPCR for the HSV-1 genome. By contrast, immunoblotting for HSV-1 antigens in purified virion preparations suggested that higher doses of Orthoquin had a physical impact on certain HSV-1 proteins that altered protein mobility or antigen detection. Orthoquin PDI also inhibited the non-enveloped adenovirus (AdV) in a dose-dependent manner, whereas Orthoquin-mediated inhibition of the enveloped vesicular stomatitis virus (VSV) was light-independent. Together, these findings suggest that the broad antiviral effects of Orthoquin-mediated PDI may stem from damage to viral attachment proteins.
- Published
- 2018
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