Enhancement of the antiviral activity of poly r(A-U) by ametantrone and mitoxantrone.
The role of ametantrone (HAQ) and mitoxantrone (DHAQ) in modulating the antiviral and interferon-inducing activities of poly r(A-U) was examined using the human foreskin fibroblast-vesicular stomatitis virus (HSF-VSV) bioassay system in which the concentration of poly r(A-U) was fixed at 0.05 mM or 0.2 mM while the HAQ or DHAQ concentration was varied to produce variable HAQ (or DHAQ)/ribonucleotide ratios ranging from 1:16 to 2:1. HAQ, DHAQ and poly r(A-U) tested individually were not efficacious antiviral agents. When poly r(A-U) was combined with the ametantrone or mitoxantrone the antiviral activity was potentiated 10-fold at HAQ (or DHAQ)/ribonucleotide ratios in the region of 1/4 to 1/6. The interferon-inducing activity of the HAQ (or DHAQ)/poly r(A-U) combinations were equal to the sum of the interferon-inducing activity of the poly r(A-U) and the HAQ (or DHAQ). These results indicate that the HAQ and DHAQ potentiate the antiviral activity of the poly r(A-U) without the superinduction of interferon. The direct viral inactivation study demonstrated that HAQ, DHAQ, poly r(A-U) and the HAQ (or DHAQ)/poly r(A-U) combinations did not inactivate the VSV at concentrations near the viral 50% inhibitory dose.
Jamison
J M
JM
Department of Chemistry, Kent State University, Ohio 44242.
Krabill
K
K
Flowers
D G
DG
Tsai
C
C
D001681:Biological Assay; D002478:Cells, Cultured; D004256:DNA Polymerase I / Q000494:pharmacology; D004357:Drug Synergism; D005347:Fibroblasts; D006801:Humans; D008942:Mitoxantrone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015394:Molecular Structure; D011063:Poly A-U / Q000494:pharmacology*; D011066:Poly C / Q000494:pharmacology; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects*
D011063:Poly A-U; D011066:Poly C; D008942:Mitoxantrone; D004256:DNA Polymerase I; C020182:ametantrone