2’-C-Methylcytidine (syn: 2CMC) is a viral replication inhibitor, shown to be active against multiple viruses including hepatitis C virus (HCV), inhibiting the HCV NS5B RNA polymerase. It is also used against other viruses including Norwalk, West Nile, dengue, foot-and-mouth, and yellow fever. The compound is a ribonucleoside analog and acts as a bioactive small molecule inhibitor of viral nucleoside polymerase.
2’-C-Methylcytidine is sparingly soluble in water.
| Application | 2’-C-Methylcytidine is useful for the development of antiviral research compounds. |
| Mechanism of Action | 2’-C-Methylcytidine has been shown to be a small-molecule inhibitor of viral nucleoside polymerase. In hepatitis C virus, it inhibits HCV NS5B RNA polymerase.
In studies with foot-and-mouth disease, experiments suggest that the compound interacts with the viral replication that coincides with the onset of intracellular viral RNA synthesis. |
| Spectrum | 2’-C-Methylcytidine can be used for multiple viruses including hepatitis C virus (HCV), Norwalk virus, and bovine pestivirus. It is also effective for three flaviviruses including yellow fever virus, West Nile virus, and dengue-2 virus. It has in vitro activity against coxsackievirus causing hand-foot-and-mouth disease and yellow fever virus. |
| Microbiology Applications | NM 283 is an efficient prodrug of 2’-C-methylcytidine. It is an 3’-O-L-valinyl ester derivative. It is a promising antiviral for HCV infection (Pierra et al, 2011).
Studies in a cell-based replicon assay indicated that several of the phosphoaramidates including NM 283 demonstrated a 10- to 200-fold potency due to higher levels of 2’-C-methylcytidine triphosphate in the cells. These prodrugs are converted to the triphosphate in hepatocytes (Gardelli et al, 2009). Dengue fever is a mosquito-borne illness that does not currently have treatment options. Nucleoside analogs that inhibit viral polymerases have shown promising antiviral activity in other viruses including Hepatitus C Virus (HCV), so in this paper Lee et al. test this antimicrobial target against the dengue virus (DENV). DENV is an RNA virus, so inhibiting the viral RNA polymerase should prove to be particularly devastating to the virus's replication. 2′-C-methylcytidine (2CMC), an analog of cytidine, was tested in vivo and in vitro, and showed promising anti-DENV activity by terminating RNA chain elongation (Lee et al, 2015). |
| Molecular Formula | C10H15N3O5 |
| References |
Gardelli et al (2009) Phosphoramidate prodrugs of 2’-C-Methylcytidine for therapy of Hepatitis C virus infection. J. Med. Chem. 52(17):5394-5407 PMID 19725579 Julander JG et al (2010) Efficacy of 2’-C-Methylcytidine against yellow fever virus in cell culture and in a hamster model. Antivir. Res. 86(3):261-267 PMID 20227442 Lee J et al (2015) Characterization of the activity of 2’-C-Methylcytidine against dengue virus replication. Antiviral Res. 116:1-9 PMID 25614455 Nesya G et al (2007) 2’-C-Methylcytidine as a potent and selective inhibitor of the replication of foot-and-mouth disease virus. Antiviral Res. 73(3):161-168 PMID 17055073 Pierra et al (2006) Synthesis and pharmacokinetics of Valopicitabine (NM283), an efficient prodrug of the potent anti-HCV agent 2'-C-Methylcytidine. J. Med. Chem. 49(22):6614-6620 PMID 17064080 Pierra C et al (2011) NM 283, An efficient prodrug of the potent anti-HCV agent 2’-C-Methylcytidine. Nucleosides, Nucleotides and Nucl. Acids 24(5-7):767-770 Rocha-Pereira JD et al (2013) The viral polymerase inhibitor 2'-C-Methylcytidine inhibits Norwalk virus replication and protects against Norovirus-induced diarrhea and mortality in a mouse model. J. Virol. 87(21):11798-1805 PMID 23986582 |
