Drug Development Against Viral Diseases (Biological Testing)
Abstract
Ribavirin and N-oxides of adenosine were two groups of nucleoside analogues which were effective in reducing mortality in Congo-Crimean hemorrhagic fever (CCHF) virus infected infant mice. A single nucleotide change in the ribavirin molecule could abrogate drug efficacy. During ribavirin treatment, virus which persisted in liver tissue was more exclusively hepatotropic than the parent virus suggesting that host-cell modified virus selection occurred. Ribavirin treatment also reduced lymphocytic choriomeningitis (LCM) virus mortality in adult mice although new drugs, including some N-oxides of adenosine, were identified which had a significantly greater effect. Both ribavirin and ara-A treatment reduced the number of tail lesions in vaccinia virus infected mice although an analogue of adenosine-N- oxide with a 3,4-dimethyl group was even more effective. Four immunomodulators significantly inhibited tail lesions in the vaccinia virus mouse model. These included quinolinamine, ampligen, recombinant II2, and poly ICLC stabilized for injection. Ribavirin did not reduce mortality of yellow fever virus infected primates,. An immunomodulator, AH (Lederle), reduced viremia as did quinolinamine which reduced both viremia and mortality. Ribavirin treatment did not eliminate skin lesions in vaccinia infected primates, but the titer of virus in vesicular scrapings was reduced. Anti-viral drugs, Vaccinia virus, Yellow fever virus, Crimean-congo hemorrhagic fever virus, RAD I.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 1992
- Accession Number
- ADB181401
Entities
People
- Gregory H. Tignor
Organizations
- Yale University