Authors: Kade Robison, David Britt, Elizabeth Vargis
Mentors: David Britt
Insitution: Utah State University
Cytomegalovirus (CMV) is the leading cause of sensorineural hearing loss, the most prevalent form of permanent hearing loss, worldwide. CMV treatment requires long term administration of nucleoside analog antivirals such as ganciclovir (GCV). Although ganciclovir effectively inhibits CMV, it also inhibits neutrophils, an essential component of the immune system, reducing optimal treatment duration. Previous studies have demonstrated that ganciclovir toxicity can be reduced while maintaining effective CMV inhibition by combining subtherapeutic doses of ganciclovir with quercetin, an FDA approved hydrophobic flavonoid with antiviral properties, solubilized with a mitochondria-targeting drug delivery vehicle, Poloxamer 188 (P188). Further efforts have been made to optimize the combinatorial ganciclovir with quercetin encapsulated in P188 (GCV-QP188) treatment by exploring the potential benefits of adding antioxidant vitamins to the GCV-QP188 treatment.
One of the pathways by which CMV induces hearing loss is the generation of excess reactive oxygen species, specifically in the mitochondria. Current literature suggests that the toxic effects of the reactive oxygen species produced by CMV in the could be reduced via natural vitamin antioxidant treatments. Ascorbic acid, also known as vitamin C, was the first antioxidant vitamin investigated due to its synergistic antiviral properties when paired with quercetin to treat SARS-CoV-2. Yet, the addition of ascorbic acid into the combinatorial treatment was more toxic than the existing GCV-QP188 treatment. Current efforts are concentrated on assessing the effect of selectively delivering hydrophobic antioxidants to the mitochondria of CMV infected mouse fibroblast cells as targeted antioxidant delivery will require lower antioxidant concentrations, reducing associated toxicity. The addition of hydrophobic antioxidants retinol and alpha-tocopherol, vitamins A and E respectively, delivered via mitochondria-targeting P188 to the existing GCV-QP188 treatment is being investigated to determine if it will significantly improve GCV-QP188 treatment efficacy.