NHC-diphosphate is an active phosphorylated intracellular metabolite of β-d-N4-Hydroxycytidine (NHC) as a diphosphate form[1]. NHC is a pyrimidine ribonucleoside and behaves as a potent anti-virus agent. NHC effectively inhibits the replication of venezuelan equine encephalitis virus (VEEV), Chikungunya virus (CHIKV) and hepatitis C virus (HCV)[1].
Huh-7 cells are incubated with (10-50 µM; 4 h) NHC or a McGuigan phosphoramidate prodrug of NHC.Intracellular levels of the parental compounds and phosphorylated metabolites are measured using LC-MS/MS. Small amounts of NHC-monophosphate (MP) and NHC-diphosphate can be observed, while NHC-triphosphate remains the most abundant metabolite.[1].
References:
[1]. Brenda I Hernandez-Santiago, et al. Metabolism of the anti-hepatitis C virus nucleoside beta-D-N4-hydroxycytidine in different liver cells. Antimicrob Agents Chemother. 2004 Dec;48(12):4636-42
[2]. Maryam Ehteshami, et al. Characterization of β-d- N4-Hydroxycytidine as a Novel Inhibitor of Chikungunya Virus.