| Summary: | 碩士 === 長庚大學 === 基礎醫學研究所 === 90 === Infections with enteroviruses cause significant morbidity and mortality in children. It is important to develop anti-enterovirus agents. Pleconaril (WIN series compounds), an anti-picornavirus capsid-binding agent, has been shown to inhibit rhinoviruses and some enteroviruses in vitro by interfering capsid-receptor binding. This potential drug has been used in clinical trial. However, pleconaril cannot neutralize the cytopathic effect (CPE) of cultured Vero and RD cells induced by enterovirus 71 (EV71). A novel class of potent and selective human enterovirus 71 inhibitor, pyridyl imidazolidinones, based on the skeleton template of WIN compounds and computer assisted drug design, had significant anti-EV71 activity. In the present study, the EV71 mutants that resistant to pyridyl imidazolidinone had been generated by serial passage in the presence of pyridyl imidazolidinones and plaque purified for genetic analysis. Four amino acid residues in the hydrophobic pocket region of VP1 were consistanting changed in the mutant strains, Tyr-116 to His, Glu-167 to Gln, Val-192 to Met and Ser-243 to Pro. These resistant mutant exhibited similar plaque morphology and growth curve to parental strains.
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