Author: Mateo, Roberto; Nagamine, Claude M.; Kirkegaard, Karla
Title: Suppression of Drug Resistance in Dengue Virus Document date: 2015_12_15
ID: 6bx2nrui_5
Snippet: To identify dominant drug targets in the dengue virus genome, we tested the effects of two different antiviral compounds: MK-0608, a nucleoside analog that inhibits the viral NS5 polymerase, and ST-148, a planar compound that inhibits the function of core protein, an oligomeric structural protein. Both in tissue culture and in mice, the selection of MK-0608-resistant viruses was readily observed. However, viruses resistant to ST-148 were not sele.....
Document: To identify dominant drug targets in the dengue virus genome, we tested the effects of two different antiviral compounds: MK-0608, a nucleoside analog that inhibits the viral NS5 polymerase, and ST-148, a planar compound that inhibits the function of core protein, an oligomeric structural protein. Both in tissue culture and in mice, the selection of MK-0608-resistant viruses was readily observed. However, viruses resistant to ST-148 were not selected in tissue culture in the presence of drug-susceptible virus, and resistant viruses did not emerge during treatment of infected mice with ST-148. Thus, dengue virus core protein is a dominant drug target, and pharmaceuticals targeted against it will be less likely to be plagued by the emergence of resistant virus.
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