Enhancement of the antiviral activity of poly r(A-U) by ametantrone and mitoxantrone

Abstract

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 humanforeskin fibroblast-vesicular stomatits 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.