Antiviral effects of ribavirin and 6-mercapto-9-tetrahydro-2-furylpurine against dengue viruses in vitro

Abstract

The antiviral effects of ribavirin (1-β- d-ribofuranosyl-1,2,4-triazole-3-carboxamide) and 6-mercapto-9-tetrahydro-2-furylpurine (6-MPTF) against dengue viruses were examined in vitro. Ribavirin significantly reduced the growth of dengue virus types 1–4 in LLC-MK2 cells at concentrations well below cytotoxic levels (cell viability was determined by trypan blue dye exclusion). Addition of guanosine to ribavirin-treated dengue virus-infected cell cultures completely reversed the antiviral effect of the drug. In contrast, ribavirin had no effect on dengue virus replication in human peripheral blood leukocytes (PBL). 6-MPTF, a specific inhibitor of hypoxanthine-guanine phosphoribosyltransferase, did not significantly reduce the growth of dengue viruses in either LLC-MK2 cells or human PBL. However, synergistic effects of 6-MPTF and ribavirin were observed, as combined treatment of the two drugs markedly suppressed the replication of dengue viruses in human PBL. The successful demonstration that dengue virus replication in mononuclear leukocytes is markedly suppressed by the combined treatment of ribavirin and 6-MPTF signals a need to evaluate the efficacy of this treatment against dengue virus infections in vivo.