BHK-21 cells persistently infected with either vaccinia or foot and mouth disease virus were used to study the efficacy of antiviral compounds. The results of the persistent infection cell culture (PICC) test were compared with those obtained by the plaque reduction (PR) test. The comparison showed that: (1) the PICC test is more informative than the PR test; (2) stimulative as well as inhibitory activities of compounds are detectable, and (3) since the PICC test can be carried on for several weeks or even months this test is especially well suited to study the problem of drug resistance in cell cultures.
The most potent drugs in the therapy of Herpes Simplex virus infections belong to the class of guanosine derivatives which bear an acyclic ether substitutent at N-9 (I,II). The initial step in the mode of action was shown to be a monophosphorylation at the primary hydroxyl group of the side chain. The selectivity of the antiviral activity results from the fact that only the virus encoded thymidine kinase is able to bind the acyclic guanosine derivatives. In order to understand this mechanism we try to describe the common pharmacophoric pattern of pyrimidine and purine substrates by molecular modeling methods. It can be shown that a specific binding of guanine could be provided by the enzyme and that flexible side chains are needed instead of deoxyribose to fulfill the requirements of the pharmacophore.
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