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Antiviral Activity of a Novel Covalently Linked Foscarnet and AZT Duplex Compound on Human Herpesvirus-6

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The title of my poster is "Antiviral Activity of a Novel Covalently Linked Foscarnet and AZT Duplex Compound on Human Herpesvirus-6". In this study a novel duplex drug consisting of covalently linked PFA and AZT (PFA-AZT) has been examined for cytotoxicity in SupT1 cells and efficacy in controlling HHV6 replication in those cells. HHV6 is a virus most known to cause exanthem subitum during childhood; latent virus has been found reactivated in immunocompromised patients and associated with many neurologic diseases such as epilepsy, multiple sclerosis (MS), encephalitis/meningitis, and post-bone marrow transplant encephalitis. Foscarnet (PFA) and AZT are both known and prescribed antivirals. PFA-AZT once characterized may serve as a new effective antiviral treatment against HHV6 and other viruses.

To begin to characterize this drug, I plated out uninfected SupT1 cells with different concentrations of PFA-AZT, measured the viability of the cells every third day and determined that the CC50 (50% Cytotoxicity Concentration) is ~60uM. I also began but have not finished an assay using HHV6-infected SupT1 cells and different concentrations of PFA-AZT to determine the IC50 (50% Inhibitory Concentration). Along with these assays to characterize the drug, I have also done a comparative study to determine if PFA-AZT is more or less effective at reducing the viral load of HHV6 in SupT1 cells. To do this I placed infected cells in a flask with concentrations of Ganciclovir and Cidofovir whose effects are known in SuptT1 cells (Akhyani et al, 2006), next to 45uM PFA-AZT. I then subcultivated the assay and took samples from each flask every third day. DNA was then extracted from each sample and quantitative real-time PCR run to determine the viral load. My results were inconclusive due to fact that the inoculum used to infect the SupT1 cells was unable to produce a thriving infection. However, another assay will be started using a different inoculum hopefully yielding conclusive results as to the efficacy of PFA-AZT compared to other known antivirals. I will continue this study and hope to find PFA-AZT to be a new and possibly more effective treatment for HHV6, a virus becoming increasingly linked with many varying neurological diseases.

Last updated February 28, 2008