Herpes simplex viruses type-1 (HSV-1) and type-2 (HSV-2) are ubiquitous human pathogens causing serious pathologies in the ocular, orofacial and anogenital regions. While current treatments such as nucleoside analogs are effective in most cases, the emergence of drug resistance necessitates the development of newer antivirals with different mechanisms of action. In this regard, BX795, a small molecule inhibitor has shown significant benefit in the treatment of herpesvirus infections previously when dosed topically. However, the efficacy of BX795's systemic dosage remains to be tested. In this study, we evaluated acute and short-term toxicity of orally administered BX795 at a concentration of 400 and 100 mg/kg respectively in mice. This was followed by an evaluation of pharmacokinetics and tissue distribution of BX795 on intravenous and oral administration. Based on these studies, we performed an in vivo antiviral study using murine models of ocular HSV-1 and genital HSV-2 infection. Our results indicate that orally administered BX795 is very well tolerated, had oral bioavailability of 56%, and reached ocular and genital tissues within the first 15 min of dosing. Our studies indicate that BX795 administered orally can significantly reduce herpesvirus replication in the ocular and genital tissue.
Keywords: Acute toxicity; Antiviral; Herpesviruses; Oral medication; Pharmacokinetic.
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