Inhibition of norovirus replication by the nucleoside analogue 2'-C-methylcytidine.

Abstract

We here report on the activity of 2'-C-methylcytidine (2CMC) [a nucleoside polymerase inhibitor of the hepatitis C virus (HCV)] on the in vitro replication of (murine) norovirus (MNV). 2CMC inhibits (i) virus-induced CPE formation, (ii) viral RNA synthesis and (iii) infectious progeny formation with EC(50) values of ∼2μM. 2CMC acts at a time-point that coincides with the onset of viral RNA synthesis. Even following 30 passages of selective pressure no MNV-resistant virus was selected, which is in line with the high barrier to resistance of the nucleoside analogue for HCV. When combined with the broad-spectrum RNA virus inhibitor ribavirin, a marked antagonistic activity was observed indicating that these molecules should not be combined for the treatment of norovirus infections. Our results suggest that 2'-C-methyl nucleoside analogues should be further explored for the treatment and prophylaxis of norovirus infections.

• Authors: J Rocha-Pereira, D Jochmans, K Dallmeier, P Leyssen, R Cunha, I Costa, M S J Nascimento, J Neyts
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 427 Issue 4 Pg. 796-800 (Nov 02 2012) ISSN: 1090-2104 [Electronic] United States
• PMID: 23063849 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Antiviral Agents
• 2'-C-methylcytidine
• Ribavirin
• Cytidine

Topics

• Animals
• Antiviral Agents (pharmacology)
• Cell Line
• Cytidine (analogs & derivatives, pharmacology)
• Drug Resistance, Viral (genetics)
• Mice
• Norovirus (drug effects, genetics, physiology)
• Ribavirin (pharmacology)
• Virus Replication (drug effects)