| Summary: | 碩士 === 國立陽明大學 === 醫學生物技術暨檢驗學系 === 102 === Enterovirus 71 (EV71) causes life-threatening diseases with neurological manifestations in young children. However, the treatment of EV71 infections remains a significantly unmet medical need. A drug screening identified IDRrubicin (IDR), an anthracycline compound, which showed anti-EV71 activities in the sub-μM range. IDR significantly protected infected cells from the cytopathic effects and cell death caused by EV71 infections. The antiviral effects can be extended to several other enterovirus species, and the effects were independent of cytotoxicity or topoisomerase inhibition. Two structural analogues, daunorubicin and epirubicin, also displayed anti-enterovirus effects, stressing the important of the core structure of this class of compounds. A time-of-addition study revealed that IDR strongly inhibited EV71 infections at 0-5 h post-infection. To unfold the mechanism of action, the anthracycline compounds were demonstrated to effectively intervene with viral protein synthesis. Moreover, these compounds were shown to suppress the virus internal ribosomal entry site (IRES)-mediated translation initiation by using a bicistronic reporter assay; conversely, IRESs present in the cellular p53 transcript were not sensitive to IDR. Competition analysis demonstrated that the degree of inhibition of IRES-mediated translation by IDR correlated well with the affinity of binding between IDR and the corresponding IRESs. This new use of anthracycline compounds as selective enteroviral IRES intercalating agents may provide new perspectives for therapeutic strategies for controlling EV71 infections and their consequences.
|
|---|
