Inhibition of norovirus replication by the nucleoside analogue 2¡ä-C-methylcytidine

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• 作者：J. Rocha-Pereira^a ; ^b ; D. Jochmans^c ; K. Dallmeier^c ; P. Leyssen^c ; R. Cunha^a ; I. Costa^a ; M.S.J. Nascimento^a ; ^b ; J. Neyts^c ; ^{Johan.Neyts@rega.kuleuven.be}
• 关键词：Norovirus ; Antiviral activity ; 2&prime ; -C-methyl nucleoside analogues ; RNA-dependent RNA polymerase
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 出版时间：2 November, 2012
• 年：2012
• 卷：427
• 期：4
• 页码：796-800
• 全文大小：359 K

文摘

We here report on the activity of 2¡ä-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 ¡«2 ¦ÌM. 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¡ä-C-methyl nucleoside analogues should be further explored for the treatment and prophylaxis of norovirus infections.