Griffiths Paul D
Centre for Virology, UCL Medical School, Rowland Hill Street, London NW3 2PF, United Kingdom.
J Clin Virol. 2009 Sep;46(1):3-8. doi: 10.1016/j.jcv.2009.06.017. Epub 2009 Jul 16.
More than 25 years after the licensure of aciclovir and then penciclovir, followed by their respective prodrugs valaciclovir and famciclovir, cases of clinically relevant resistance to these drugs in immunocompetent individuals remain very rare. The aim of this review is to focus on the mechanism of action of these anti HSV drugs and then briefly compare this favourable outcome with that of CMV, HIV, HBV and influenza. A central theme is that resistance is an epiphenomenon of failure to suppress virus replication, so that improved potency and selectivity should be prioritised when developing new drugs rather than activity against resistant strains per se.
在阿昔洛韦和喷昔洛韦获批上市25年多后，紧接着它们各自的前体药物伐昔洛韦和泛昔洛韦也获批上市，在免疫功能正常的个体中，对这些药物产生临床相关耐药性的病例仍然非常罕见。本综述的目的是聚焦于这些抗单纯疱疹病毒药物的作用机制，然后简要地将这一良好结果与针对巨细胞病毒、人类免疫缺陷病毒、乙型肝炎病毒和流感病毒的情况进行比较。一个核心主题是，耐药性是未能抑制病毒复制的一种附带现象，因此在开发新药时，应优先考虑提高效力和选择性，而不是针对耐药菌株的活性本身。
