Abstract：
:Venezuelan equine encephalitis virus (VEEV) may cause encephalitis in humans, for which no FDA-approved antiviral treatment is available. Carbocyclic cytosine (carbodine) has broad-spectrum activity but toxicity has limited its utility. It was anticipated that one of the enantiomers of carbodine would show enhanced activity and reduced toxicity. The activity of the d-(-) enantiomer of carbodine [(-)-carbodine] was evaluated by infectious cell culture assay and was found to have a 50% effective concentration (EC50) of 0.2 microg/ml against the TC-83 vaccine strain of VEEV in Vero cells, while the l-(+) enantiomer had no activity. Virus titer inhibition correlated with intracellular cytidine triphosphate reduction after treatment with (-)-carbodine, as determined by HPLC analysis. Pre-treatment with 200 mg/(kgd) resulted in significant improvement in survival, virus load in the brain, weight change, and mean day-to-death in a mouse model of TC-83 VEEV disease. A single dose of (-)-carbodine resulted in a slight extension of mean time to death in mice infected with wild-type VEEV. Post-virus exposure treatment with (-)-carbodine was effective in significantly improving disease parameters in mice infected with TC-83 VEEV when treatment was initiated as late as 4 days post-virus installation (dpi). It is remarkable that (-)-carbodine is effective when initiated after the establishment of brain infection.
journal_name
Antiviral Resjournal_title
Antiviral researchauthors
Julander JG,Bowen RA,Rao JR,Day C,Shafer K,Smee DF,Morrey JD,Chu CKdoi
10.1016/j.antiviral.2008.07.002subject
Has Abstractpub_date
2008-12-01 00:00:00pages
309-15issue
3eissn
0166-3542issn
1872-9096pii
S0166-3542(08)00356-2journal_volume
80pub_type
杂志文章abstract：:Lentiviral vectors have been shown to be good candidates for gene transfer protocols; however, prevention of insertional mutagenesis remains problematic. Here we report on the design of a conditionally replicating integrase (IN)-defective lentiviral-hybrid episomal vector in which the insertion of the SV40 promoter/or...
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pub_type： 杂志文章,评审
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更新日期：2013-05-01 00:00:00
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更新日期：2003-05-01 00:00:00
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journal_title：Antiviral research
pub_type： 杂志文章,评审
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更新日期：1999-02-01 00:00:00
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