2′-C-β-Methylguanosine

2’-C-β-Methylguanosine is an active nucleoside metabolite of the antiviral prodrug BMS-986094.¹ It inhibits replication in genotype 1b hepatitis C virus (HCV) replicon cells (EC₅₀s = 5.2 and 3.2 µM in ELISA and luciferase assays, respectively).² 2’-C-β-Methylguanosine also inhibits replication of the Zika virus clinical isolate ZIKV_PE243 in infected human brain microvascular endothelial cells (HBMECs), SH-SY5Y cells, and Vero cells (EC₅₀s = 0.88, 2.09, and 1.25 µM, respectively) but is toxic to mice infected with ZIKV_PE243 at postnatal day 2 when administered at a dose of 25 mg/kg per day.³

1.Liu, A., Lute, J., Gu, H., et al.Challenges and solutions in the bioanalysis of BMS-986094 and its metabolites including a highly polar, active nucleoside triphosphate in plasma and tissues using LC-MS/MSJ. Chromatogr. B Analyt. Technol. Biomed. Life Sci.100029-40(2015) 2.Sizun, G., Pierra, C., Peyronnet, J., et al.Design, synthesis and antiviral evaluation of 2’-C-methyl branched guanosine pronucleotides: The discovery of IDX184, a potent liver-targeted HCV polymerase inhibitorFuture Med. Chem.7(13)1675-1700(2015) 3.Matos de Souza, M.R., Cunha, M.S., Okon, A., et al.In vitro and in vivo characterization of the anti-Zika virus activity of ProTides of 2’-C-β-methylguanosineACS Infect. Dis.6(7)1650-1658(2020)