Melby Tom, Westby Mike
Clinical Virology Associates, 101 E. Ellerbee St. Durham, NC 27704, USA.
Handb Exp Pharmacol. 2009(189):177-202. doi: 10.1007/978-3-540-79086-0_7.
The entry of viruses into target cells involves a complex series of sequential steps, with opportunities for inhibition at every stage. Entry inhibitors exert their biological properties by inhibiting protein-protein interactions either within the viral envelope (Env) glycoproteins or between viral Env and host-cell receptors. The nature of resistance to entry inhibitors also differs from compounds inhibiting enzymatic targets due to their different modes of action and the relative variability in Env sequences both temporally and between patients. Two drugs that target HIV-1 entry, enfuvirtide and maraviroc, are now licensed for treatment of HIV-1 infection. The efficacy of these drugs validates entry as a point of intervention in viral life cycles and, in the context of HIV treatment, contributes to the growing armamentarium of antivirals which, in multidrug combinations, can effectively inhibit viral replication and prevent disease progression.
病毒进入靶细胞涉及一系列复杂的连续步骤，在每个阶段都存在被抑制的可能性。进入抑制剂通过抑制病毒包膜（Env）糖蛋白内部或病毒Env与宿主细胞受体之间的蛋白质-蛋白质相互作用来发挥其生物学特性。由于其不同的作用方式以及Env序列在时间上和患者之间的相对变异性，对进入抑制剂的耐药性性质也与抑制酶靶点的化合物不同。两种靶向HIV-1进入的药物，恩夫韦肽和马拉维罗，现已获批用于治疗HIV-1感染。这些药物的疗效证实了进入作为病毒生命周期中的一个干预点，并且在HIV治疗中，有助于不断增加的抗病毒药物库，这些药物在多药联合使用时可以有效抑制病毒复制并预防疾病进展。
