定義四環黴素衍生物抑制登革熱二型病毒的功能性成分

Abstract

登革熱是世界上熱帶和亞熱帶地區常見的主要疾病，被認為是節肢動物所引發最重要的病毒性疾病之一。每年有超過五千萬到一億的人口會感染登革熱，散布範圍遍佈一百多個國家。過去的研究中，主要都在登革熱疫情擴張和開發疫苗，以及針對病毒的複製酵素研發抑制劑。但在一般市面上仍然沒有商業化的登革熱藥物或疫苗可用。先前本實驗室已經發現特定四環素衍生物可有效抑制登革熱病毒。但是並非所有四環素衍生物都可有效抑制病毒。推測四環黴素上的立體結構或側鏈為抑制病毒複製的主要原因。根據實驗室前人的研究成果，我分析出四個可能是藥物有效的規則。並且使用這些規則來選擇一系列的四環素衍生物或類似物來檢測它們對病毒感染力的影響。數據顯示，這系列藥物都具有病毒抑制力，也對於登革熱病毒二型有相當高的專一性。此外，我利用免疫螢光標記檢測病毒蛋白在寄主內的情形及細胞核的狀態。結果證實，我們選擇的這些藥物具有抑制效果且對細胞沒有毒性。綜合上述結果，藥物篩選規則已經有個雛型。後續則須更多的實驗來檢測這種假設。

Dengue fever has become a major global health issues in tropical and subtropical regions. And it is considered the most important arthropod-born viral disease affecting humans in terms of morbidity and mortality. About 50-100 million cases of illnesses occur each year, and more than 100 countries have endemic dengue transmission. In previous works, researchers focused on dengue prevention and vaccine, and some targeted the enzymes for dengue replication. But there are still no commercial available drugs or vaccines for dengue disease. Previously, our laboratory has discovered that tetracycline derivatives can be need as inhibitors on dengue viruses. But not all of tetracycline derivatives are effective on the virus. Based on previous resuls, I selected a series of tetracycline derivatives and analogues to determine their effect on virus infectivity. My result shows all tested tetraccyclines have inhibitory effects on DV to various extent. Their effect on dengue virus serotypeⅡ is specific. In addition, I use immunofluorescence labeling detect to the presence of viral protein in the hosts and the presence of host nuclei. The results confirmed that the drugs have inhibitory effect on DV and low toxicity to the host cell.