Drug Development Against Viral Diseases
Abstract
One hundred fifty drugs have been tested for efficacy against CCHF (strain 10200). Sixteen percent of the drugs tested had VR (virus rating) scores greater than 1.5. Ten percent had VR scores greater than 1.8. An additional twelve drugs tested were found to be toxic at 50 mg/kg and in many cases at all levels tested, some as low as 0.25 mg/kg. The total number of drugs tested for toxicity in the CCHF model was one hundred sixty-two. The sensitivity of the CCHF test system was monitored by inclusion of the positive drug, ribavirin, AVS 1. The VR+ value was compared after 19 tests. The mean VR+ was 2.6 with standard deviation of 0.6. Tests were done with selected drugs to determine the effect of virus dose on VR scores using 50 and 5 LD50's of virus. The correlation between VR scores at the two dose levels was close with ineffective drugs. In contrast, with drugs giving a high VR score at 50 LD50's, the correlation at 5 LD50's was less close. However, there was little variation using the VR+ control drug, ribavirin. The pathogenesis of CCHF virus in infant mice was determined by titrating virus daily from virus-infected mice and from ribavirin-treated mice using blood, liver, brain, spleen, and heart. Nine drugs were tested in a rabies virus model of intramuscular infection. Viremia levels were determined using sera from yellow fever virus infected and ribavirin-treated primates (squirrel monkeys). Keywords: Anti-viral drug, Lymphocytic choriomeningitis virus, Crimean-Congo hemorrhagic fever virus, Yellow fever virus.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 1988
- Accession Number
- ADA206925
Entities
People
- Gregory H. Tignor
Organizations
- Yale University