Inhibition of bluetongue and Colorado tick fever orbiviruses by selected antiviral substances

Abstract

The effects of four ribonucleic acid virus inhibitors were evaluated in cell cultures and in mice to determine inhibitory effects against bluetongue virus and Colorado tick fever virus (CTFV). Test compounds included 1-/-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin), 3-deazaguanine, 3-deazauridine, and 9-(S)-(2,3-dihydroxypropyl)adenine. Ribavirin-2',3',5'-triacetate (ribavirin triacetate) was evaluated in vivo against CTFV. Inhibition of cytopathic effect and plaque reduction were used to evaluate antiviral activity. In cytopathic effect inhibition studies, bluetongue virus was markedly inhibited by 3-deazaguanine and 3-deazauridine in Vero cells with moderate inhibition by the other agents. Ribavirin and 3-deazaguanine markedly inhibited CTFV in MA-104 cells, 3-deazauridine was slightly less active, and 9-(S)-(2,3-dihydroxypropyl)adenine was negative. Ribavirin was less effective in Vero cells against CTFV. When mice were inoculated intracerebrally with CTFV and treated by a single intracerebral injection with drug, ribavirin triacetate increased the number of survivors, 3-deazaguanine increased mean survival time, and ribavirin was negative. Intraperitoneal treatment of infected mice with ribavirin triacetate for 1 week significantly increased the number of survivors and mean survival time, providing strong evidence that the agent is active across the blood-brain barrier.

Treatment of intracranial dengue virus infections in mice with a lipophilic derivative of ribavirin

“…Because of its greater lipid solubility, RTA is more likely to pass through the blood-brain barrier and may act as a prodrug which is slowly hydrolyzed to ribavirin itself in vivo (2). Studies by Smee et al (10) with Colorado tick fever virus infections supported this hypothesis of the propensity of RTA to cross the blood-brain barrier and suppress viral encephalitic disease. Our study demonstrates that RTA exhibits significant antiviral efficacy against dengue virus infections intracranially in mice when the drug is administered i.p.…”

Targeting drugs to the brain by redox chemical delivery systems

“…203±205 The rationale behind the consideration of making a CDS was that esteri®cation would enhance hydrophobicity and improve CNS penetration. Triacetyl 206,207 and tributyryl 208 derivatives of 50 (prodrugs) increased the survival time and number of survivors after intracerebral inoculation of animals with viruses against which 50 itself was ineffective. The parent compound has three OH groups (2 H , 3 H , and 5 H positions) that are suitable for derivatization; one for placing the T moiety and the rest can be masked with lipophilicityenhancing groups to further facilitate the brain delivery.…”

Discovery of Novel Ribonucleoside Analogs with Activity against Human Immunodeficiency Virus Type 1

“…Our study, to the best of our knowledge, is the first to demonstrate the antiretroviral activity of formycin A. Many previous studies identified the activity of 3-deazauridine against riboviruses (20)(21)(22)(23)(24)(25)(26) and retroviruses (23,27). Interestingly, 3-deazauridine was previously observed to potentiate the anti-HIV-1 activity of 3TC and dideoxycytosine (28).…”