
Effects of selenazofurin and ribavirin and their 5'-triphosphates on replicative functions of influenza A and B viruses
Author(s) -
S K Wray,
R. H. A. Smith,
Brian E. Gilbert,
Ver Knight
Publication year - 1986
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.29.1.67
Subject(s) - ribavirin , virology , primer (cosmetics) , biology , polymerase , viral replication , nucleoside triphosphate , virus , rna polymerase , rna , orthomyxoviridae , influenza a virus , microbiology and biotechnology , biochemistry , dna , chemistry , nucleotide , gene , hepatitis c virus , organic chemistry
We studied the effects of selenazofurin alone and in combination with ribavirin on replication of influenza A and B viruses. These drugs showed little cytotoxicity as measured by leucine incorporation into protein in MDCK cells, although they were potent inhibitors of viral replication in the same cells. Selenazofurin inhibited growth of influenza A and B viruses at concentrations (50% inhibitory dose = 25 and 19 microM, respectively) which were similar to those at which growth was inhibited by ribavirin (50% inhibitory dose = 50 and 30 microM, respectively). The inhibition of replication of either influenza A or B virus was additive for any combination of ribavirin and selenazofurin. The effects of the 5'-triphosphate of selenazofurin on two replicative functions associated with the influenza virus RNA-dependent RNA polymerases, primer generation (initiation of transcription) and its subsequent elongation, were measured. Elongation was more sensitive to selenazofurin 5'-triphosphate than was primer generation, and the effects of this drug on these functions were approximately the same as those of ribavirin 5'-triphosphate. The activities of ribavirin triphosphate and selenazofurin triphosphate were additive, and combinations did not potentiate the individual inhibitory effects of these drugs on elongation.