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

Article Details

Citation

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

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

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

PubMed ID
15890415 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
KP-1461Gag-Pol polyproteinProteinHIV-1
Unknown
Not AvailableDetails