神經胺酸酶是存在於流感病毒表面的醣蛋白,在病毒進行感染過程中扮演重要的角色,因此常被視為具潛力的抑制目標,以進行流感藥物的開發。近年來為了控制流感的蔓延,修飾抑制分子的化學結構達到有效抑制神經胺酸酶活性的研究變得十分熱門。本篇專題輔導將回顧一系列成功設計神經胺酸酶抑制分子的研究歷程,其中包含已成為現行治療的兩種藥物(克流感和瑞樂沙),與一些正進行臨床治療試驗的流感候選藥物(聚合化的Zanamivier BCX-1812和乙脂化的ABT-675等潛力抑制分子)。在本篇報導我們同時回顧以電腦分子模擬技術,預測設計的不同骨架化學結構分子對抑制神經胺酸酶的機制。
Neuraminidase, an important surface glycoprotein of influenza virus, is essential for the viral infection, and thus a target for anti-influenza drug development. The extensive research of the structure- and mechanism-based neuraminidase inhibitors has led to a breakthrough in the development of effective drugs for control of influenza epidemics. This review will cover the successful designs and processes in the development of neuraminidase inhibitors. Two drugs Tamiflu and Relenza are available as prescription drugs, and some promising drugs, such as polymeric Zanamivir, BCX-1812 and ABT-675 ethyl ester, are currently in clinical trials. The molecular-modeling techniques are applied to study the mechanism of drug action, and to predict the inhibition potency of neuraminidase.