Antiviral Res. 2005 Jul;67(1):1-9.

KP-1212/1461, a nucleoside designed for the treatment of HIV by viral mutagenesis.

Harris KS, Brabant W, Styrchak S, Gall A, Daifuku R.

Source

Koronis Pharmaceuticals Inc., 12277 134th Ct. N.E. Redmond, WA 98052, USA. kharris@koronispharma.com

Abstract

We report the activities of a novel nucleoside analog against HIV. This nucleoside (KP-1212) is not a chain terminator but exerts its antiviral effects via mutagenesis of the viral genome. Serial passaging of HIV in the presence of KP-1212 causes an increase in the mutation rate of the virus leading to viral ablation. HIV strains resistant to KP-1212 have not yet been isolated. Quite to the contrary, virus treated with KP-1212 exhibited an increased sensitivity not only to KP-1212 but also to another nucleoside reverse transcriptase inhibitor (NRTI), zidovudine. HIV strains resistant to other NRTIs (e.g. zidovudine, lamivudine, stavudine, abacavir, etc.) exhibited no cross-resistance towards KP-1212. Multiple assays confirmed that KP-1212 has a favorable (low) genotoxicity profile when compared to some approved antiviral nucleosides. In addition, KP-1212 is not toxic to mitochondria nor does it exhibit any inhibitory effects on mitochondrial DNA synthesis.

PMID:: 15890415; [PubMed - indexed for MEDLINE]

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