Document Detail


In vitro antiviral activity of mycophenolic acid and its reversal by guanine-type compounds.
MedLine Citation:
PMID:  4308535     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
With the agar diffusion test and BS-C-1 cells, mycophenolic acid was found to give a straight-line dose-response activity in inhibiting the cytopathic effects of vaccinia, herpes simplex, and measles viruses. Plaque tests have shown 100% reduction of virus plaques by mycophenolic acid over drug ranges of 10 to 50 mug/ml and virus input as high as 6,000 plaque-forming units (PFU) per flask. Back titration studies with measles virus inhibited by mycophenolic acid have indicated that extracellular virus titers were reduced by approximately 3 logs(10) and total virus was reduced by 1 log(10). The agar diffusion test system lends itself readily to drug reversal studies. Mycophenolic acid incorporated into agar at 10 mug/ml gave 100% protection to virus-infected cells. Filter paper discs impregnated with selected chemical agents at concentrations of 1,000 mug/ml (20 mug per filter paper disc) were placed on the agar surface. Reversal of the antiviral activity of mycophenolic acid was indicated by virus breakthrough in those cells in close proximity to the filter paper disc. Chemicals showing the best reversal of the antiviral activity of mycophenolic acid were guanine, guanosine, guanylic acid, deoxyguanylic acid, and 2,6-diaminopurine. The reversal of antiviral activity was confirmed by titrations of virus produced with various amounts of both mycophenolic acid and guanine present and by isotope tracer methods with uptakes of labeled uridine, guanine, leucine, and thymidine in treated and nontreated, infected and noninfected cells as parameters. All antiviral effects of mycophenolic acid at 10 mug/ml could be reversed to the range shown by untreated controls by the addition of 10 mug/ml of those chemicals exhibiting reversal activity.
Authors:
J C Cline; J D Nelson; K Gerzon; R H Williams; D C Delong
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Applied microbiology     Volume:  18     ISSN:  0003-6919     ISO Abbreviation:  Appl Microbiol     Publication Date:  1969 Jul 
Date Detail:
Created Date:  1969-10-05     Completed Date:  1969-10-05     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7605802     Medline TA:  Appl Microbiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  14-20     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Caproates / antagonists & inhibitors,  blood,  pharmacology*
Cell Line
Cytopathogenic Effect, Viral
Guanine / pharmacology
Guanine Nucleotides / pharmacology
Haplorhini
Kidney
Measles virus / drug effects*
Methods
Mice
Nucleosides / pharmacology
Simplexvirus / drug effects*
Vaccinia virus / drug effects*
Chemical
Reg. No./Substance:
0/Caproates; 0/Guanine Nucleotides; 0/Nucleosides; 73-40-5/Guanine
Comments/Corrections

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