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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1989-9-28
pubmed:abstractText
The antiviral activities of ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide; virazole), either alone or in combination with recombinant human leukocyte (alpha) interferon (rHuIFN-alpha), were evaluated against feline infectious peritonitis virus (FIPV) in feline kidney-cell cultures. The 50% inhibitory dose (ID50) of ribavirin for uninfected, rapidly dividing cells was approximately 17 micrograms ml-1 whereas the ID50 for FIPV was 2.5 micrograms ml-1. The therapeutic index (TI) of ribavirin (i.e. the ratio of the minimum cell-toxic dose to minimum virus-inhibitory dose) was 6.8. Although a dose-dependent inhibition of viral infectivity occurred at non-toxic doses, maximum antiviral effects (greater than or equal to 4 log10 reduction in FIPV) occurred at cytotoxic doses. When low or moderate doses of ribavirin were combined with either 10 or 100 U of rHuIFN-alpha ml-1, the resulting antiviral effects were significantly greater than the sum of the observed effects from either ribavirin or rHuIFN-alpha alone. Significant synergistic interactions with rHuIFN-alpha occurred at ribavirin doses of 1, 5, 12.5 and 25 micrograms ml-1. Synergistic combinations of rHuIFN-alpha and ribavirin produced up to an 80-fold or a 200-fold relative increase in FIPV antiviral activities compared with that produced by equivalent doses, respectively, of ribavirin or rHuIFN-alpha alone. In cell growth studies, the addition of either 10 or 100 U of rHuIFN-alpha ml-1 to test doses of ribavirin did not increase the anticellular effect observed with ribavirin alone; seemingly, the potentiation of ribavirin antiviral activity by rHuIFN-alpha was independent of any additive cytotoxic effects. Potentially, synergistic combinations of the two antiviral agents in vivo may decrease the therapeutic dose of ribavirin required for inhibition of FIPV and thus reduce drug toxicity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0378-1135
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
255-65
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Inhibitory effects of ribavirin alone or combined with human alpha interferon on feline infectious peritonitis virus replication in vitro.
pubmed:affiliation
Scott-Ritchey Research Program, College of Veterinary Medicine, Auburn University, AL 36849.
pubmed:publicationType
Journal Article