final program.qxd - Parallels Plesk Panel
final program.qxd - Parallels Plesk Panel
final program.qxd - Parallels Plesk Panel
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FP 0.1<br />
Thiovir exhibits broad-spectrum antiviral activity against human and avian<br />
influenza viruses, human immunodeficiency viruses, and herpes simplex viruses<br />
Shani Waninger, Silvestre Ramos and Joan Robbins<br />
Adventrx Pharmaceuticals, San Diego, CA 92121, USA<br />
Objective<br />
Thiovir (thiophosphonoformic acid) is a prodrug of the broad-spectrum antiviral-drug<br />
foscarnet (phosphonoformic acid). Foscarnet currently has limited therapeutic usage, in<br />
part because of its intravenous route of delivery. In contrast, Thiovir has increased<br />
bioavailability that enables oral delivery. Based on the broad-spectrum activity of<br />
oscarnet, we examined the antiviral activity of Thiovir against multiple virus types,<br />
including human and avian influenza, human immunodeficiency virus (HIV) and herpes<br />
simplex viruses (HSV).<br />
Methods<br />
Antiviral activity of Thiovir and foscarnet was tested using in vitro viral infection assays.<br />
Activity against influenza virus infection of MDCK cells was determined by either a plaque<br />
assay or ELISA. Anti-HIV activity was determined by the PhenoSense assay. Activity<br />
against HSV infection of Vero cells was determined by a plaque assay. In all assays, cells<br />
were pre-incubated with drugs for approximately 30 minutes before virus addition.<br />
Results: We observed dose-dependent antiviral activity of Thiovir against multiple<br />
subtypes of human and avian influenza A and human influenza B virus. Similarly, Thiovir<br />
inhibited two types of herpes simplex virus, HSV-1 and HSV-2. Thiovir was also active<br />
against multiple HIV-1 clades, HIV-2, and HIV strains resistant to current antiretroviral<br />
therapies. For all virus types, the level (IC50) of antiviral activity for Thiovir was similar to<br />
foscarnet.<br />
Conclusions<br />
Thiovir demonstrated effective and broad-spectrum antiviral activity against HIV, HSV, and<br />
human and avian influenza viruses in vitro. The broad activity, combined with the<br />
increased oral bioavailability, suggests Thiovir may have an increased therapeutic<br />
advantage compared to foscarnet. Furthermore, the antiviral activity of Thiovir against<br />
human and avian influenza suggests Thiovir may have applications in the event of global<br />
bird flu pandemic.<br />
POSTERS<br />
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