Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 427, Issue 4, Pages 796-800Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2012.10.003
Keywords
Norovirus; Antiviral activity; 2 '-C-methyl nucleoside analogues; RNA-dependent RNA polymerase
Categories
Funding
- European Union [FP7/2007-2013]
- SILVER [260644]
- KULeuven GOA [GOA/10/014]
- Fundacao para a Ciencia e Tecnologia [SFRH/BD/48156/2008]
- U. Porto
- Fundação para a Ciência e a Tecnologia [SFRH/BD/48156/2008] Funding Source: FCT
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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 EC50 values of similar to 2 mu M. 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. (C) 2012 Elsevier Inc. All rights reserved.
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