Rna-intercalating Agent Interactions: In Vitro Antiviral Activity Studies

Rna-intercalating Agent Interactions: In Vitro Antiviral Activity Studies

Jamison J M; Krabill K; Allen K A; Stuart S H; Tsai C C

Antiviral Chemistry & Chemotherapy

1990

1990-12

Twenty intercalating agents were tested to examine the effects of intercalating dye-induced perturbations upon the antiviral activity of poly (adenylate-uridylate) [poly (A-U)]. Neither poly (A-U) alone nor each intercalative dye was an efficacious antiviral agent. When poly (A-U) was combined with major groove intercalating dyes (acridine orange or proflavine), no synergism was observed. When poly (A-U) was combined with minor groove intercalating dyes [ethidium (EB), propidium (PI), adriamycin (ADR) or daunomycin (DMN)] or minor/major groove intercalating dyes [9-aminoacridine (9-AA), N-2-methyl-9-hydroxy-ellipticine (NMHE) or N-2,N-6-dimethyl-9-hydroxy-ellipticine (DMHE)] the 50% effective doses (ED50) of the poly (A-U), 9-AA, ADR, DMHE, DMN, EB, NMHE and PI decreased 18-, 22-, 60-, 274-, 61-, 154-, 113- and 299-fold, respectively. When poly (A-U) was combined individually with 11 dyes whose mode of intercalation was not known, the ED50 of ametantrone (HAQ), chloroquine (CHL), mitoxantrone (DHAQ) and quinine (QUI) decreased 125-, 65-, 251- and 32-fold, respectively. These results suggest that the four dyes may intercalate into poly (A-U) from the minor groove. Ten (ADR, CHL, DMN, DHAQ, DMHE, EB, HAQ, NMHE, PI, QUI) of the 20 dyes evaluated exhibited significant synergism with poly (A-U), as quantified by the fractional inhibitory concentration index. Interferon (IFN) neutralization assays demonstrated that the IFN-inducing capability of the dye/poly (A-U) combinations approximated the sum of the capabilities of the poly (A-U) and the dyes employed. These results suggest that the majority of the dyes tested potentiate the antiviral activity of poly (A-U) without affecting the amount of IFN induced.

Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Virology

Journal Article or Conference Abstract Publication

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

333-347

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