Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Photodynamic Inactivation of Herpes Simplex Viruses

Version 1 : Received: 6 September 2018 / Approved: 7 September 2018 / Online: 7 September 2018 (05:26:24 CEST)

A peer-reviewed article of this Preprint also exists.

Monjo, A. .-A.; Pringle, E.S.; Thornbury, M.; Duguay, B.A.; Monro, S.M.A.; Hetu, M.; Knight, D.; Cameron, C.G.; McFarland, S.A.; McCormick, C. Photodynamic Inactivation of Herpes Simplex Viruses. Viruses 2018, 10, 532. Monjo, A. .-A.; Pringle, E.S.; Thornbury, M.; Duguay, B.A.; Monro, S.M.A.; Hetu, M.; Knight, D.; Cameron, C.G.; McFarland, S.A.; McCormick, C. Photodynamic Inactivation of Herpes Simplex Viruses. Viruses 2018, 10, 532.

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 pre-mature 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 broad antiviral effects of Orthoquin-mediated PDI may stem from damage to viral attachment proteins.

Keywords

HSV-1; HSV-2; photodynamic inactivation; plaque assay; natural product; antiviral

Subject

Biology and Life Sciences, Virology

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