Effects of Ribamidine, a 3-Carboxamidine Derivative of Ribavirin, on Experimentally Induced Phlebovirus infections

Document Type

Article

Journal/Book Title/Conference

Effects ofribamidine, a 3-carboxamidine derivative of ribavirin on experimentally-induced Phlebovirusinfections

Volume

10

Publication Date

1989

First Page

193

Last Page

208

Abstract

Ribamidine (1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine) was inhibitory in rhesus monkey kidney (LLC-MK2 derivative) cells to Adames and Balliet strains of Punta Toro virus (PTV), a Phlebovirus related to Rift Valley fever and sandfly fever viruses. The 50% effective dose was 8 and 12 μg/ml against each respective virus strain; the 50% cytotoxic dose was 320 μg/ml, giving selectivity indices of 40 and 27 against each virus strain. The virus ratings were 1.2 and 1.0, respectively. In radiolabel uptake studies, ribamidine had a moderate effect on [3H]leucine uptake at dosages down to 1 μg/ml, but [3H]thymidine, [32P], and [3H]uridine were inhibited at high (100–1000 μg/ml) doses only. Subcutaneous (s.c.) and oral treatments of Adames PTV-infected mice were equally highly effective, as evidenced particularly by 100% survivors. Reduced hepatic icterus, serum oxalic acid transaminase, serum glutamic pyruvic acid transaminase, and recoverable virus titers from livers and sera of infected mice were also seen as a result of ribamidine treatment. Twice daily treatment for 5 days could be started as late as 72 h post-virus inoculation (p.v.i.) with significant inhibition of PTV infection seen. Single s.c. treatments administered as late as 48 h p.v.i. were similarly effective. Using the chronic therapy schedule, the maximum tolerated dose was 1000 mg/kg/day and the minimum effective dose was 31.3 to 62.5 mg/kg/day. Using single treatment, a maximum tolerated dose was >1000 mg/kg, and the minimum effective dose was 125 mg/kg. Ribamidine s.c. treatment of mice infected intracerebrally with the Balliet strain of PTV resulted in a moderate infection-inhibitory effect, seen especially by reduced virus titers in the brains of the infected, treated mice.

Comments

Antiviral Res. 10: 193-208. PMID: 2976263

Link to Full Text

Share

COinS