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Antiviral activity of nucleoside analogues against norovirus.
MedLine Citation:
PMID:  22910194     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Norovirus (NoV) is the leading cause of epidemic gastroenteritis worldwide. The lack of a cell culture has significantly hampered the development of effective therapies against human NoV. Clinically approved nucleoside and non-nucleoside analogues have been used successfully against RNA viruses. METHODS: In this study, we evaluated the efficacy of four nucleoside analogues (2'-C-MeC, 2'-F-2'-C-MeC, β-D-N(4)-hydroxycytidine [NHC] and lamivudine) on Norwalk virus (NV) RNA levels and protein expression in NV replicon-harbouring cells (HG23 cells), and their efficacy in blocking murine norovirus (MNV) replication in RAW 264.7 cells. RESULTS: 2'-C-MeC and 2'-F-2'-C-MeC reduced MNV RNA levels and infectivity in RAW 264.7 cells in a concentration- and time-dependent manner. The median effective concentrations (EC(50)) of 2'-C-MeC and 2'-F-2'-C-MeC were 6.9 μM and 12.7 μM, respectively. 2'-C-MeC, 2'-F-2'-C-MeC and NHC reduced NV RNA levels and protein expression in HG23 cells. For the NV replicon, the EC(50) of 2'-C-MeC (1.3 μM) was comparable to the antiviral activity of NHC (1.5 μM) and twofold more potent than 2'-F-2'-C-MeC (3.2 μM). The combination of 2'-C-MeC/ribavirin resulted in modest synergistic activity, whereas NHC/ribavirin was antagonistic for NV replication in HG23 cells. CONCLUSIONS: The antiviral activity of 2'-C-MeC against strains of two different NoV genogroups and the low EC(50) suggest that this nucleoside analogue may be effective against the more prevalent GII NoVs. In the absence of a vaccine, antiviral agents could be an effective intervention to control the spread of human NoV in populations at a high risk for NoV disease.
Authors:
Verónica P Costantini; Tony Whitaker; Leslie Barclay; David Lee; Tamara R McBrayer; Raymond F Schinazi; Jan Vinjé
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-14
Journal Detail:
Title:  Antiviral therapy     Volume:  -     ISSN:  2040-2058     ISO Abbreviation:  Antivir. Ther. (Lond.)     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815705     Medline TA:  Antivir Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA. vcostantini@cdc.gov.
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