(adapted from applicant's abstract) The investigators have developed a rapid and inexpensive method to screen for antiviral and anti-proliferative drugs based upon inhibition of Chlorella virus (Cvi) plaque proliferation on nutrient agar plates. It is by virtue of their ability to detect inhibitors of DNA polymerase, ribonucleotide reductase, Inosine monophosphate (IMP) Dehydrogenase, DNA topoisomerase II, and viral lipid synthesis, that the investigators propose its use as a method for antiviral/anti-proliferative drug screening. Thus, it is the objective during the Phase I feasibility period to: i) determine if the antiviral activity of aphidicolin and mycophenolic acid be detected in crude extracts of culture fluid from Cephalosporium aphidicola and Penicillium brevi-compactum, ii) determine if Chlorella virus plaque inhibition assays can be used to identify synthetic inhibitors of ribonucleotide reductase. In particular, the model compound to be tested are the synthetic heterocyclic thiosemicarbazones, which are inhibitors of ribonucleotide reductase, and iii) determine if the plaque inhibition assays can be automated. In particular, can test compounds be spotted from 8 x 12 plastic microtiter wells onto antiviral test plates.
Thesaurus Terms:DNA virus, drug screening /evaluation, method development, plaque assay antiviral agent, aphidicolin, biological product, biomedical automation, chemical synthesis, growth inhibitor, mycophenolic acid, synthetic protein, thiosemicarbazone colorimetry, microorganism cultureNational Institute of Allergy and Infectious Diseases (NIAID)
