Hasegawa T, Kurokawa M, Yukawa T A, Horii M, Shiraki K
Department of Virology, Toyama Medical and Pharmaceutical University, Japan.
Antiviral Res. 1995 Jun;27(3):271-9. doi: 10.1016/0166-3542(95)00007-9.
Penciclovir has potent antiviral activity against varicella-zoster virus (VZV). We have characterized the inhibitory effects of penciclovir and acyclovir on the plaque formation of cell-free VZV and cross-resistance of acyclovir-resistant VZV to penciclovir. The apparent effective concentration for 50% plaque reduction (EC50) of penciclovir determined on the third day was significantly lower than that determined on the fourth or fifth day. The size of plaques was smaller in the presence of penciclovir than in the presence of acyclovir. The effective concentrations for 50% reduction of the number of infected cells per plaque were 1.40 and 5.00 micrograms/ml for penciclovir and acyclovir, respectively. Thus penciclovir suppressed spread of infection within developing plaques more efficiently than acyclovir. Five acyclovir-resistant VZV strains with altered DNA polymerase selected by acyclovir were examined for cross-resistance to penciclovir. They were 11- to 18-fold more resistant to ACV than the parent strain, but only 4- to 5-fold more resistant to PCV. Penciclovir-triphosphate carrying the 3'-hydroxyl group of 2'-deoxyribose might have better affinity to the altered viral DNA polymerase than acyclovir-triphosphate without the 3'-hydroxyl group.
喷昔洛韦对水痘带状疱疹病毒（VZV）具有强大的抗病毒活性。我们已经阐明了喷昔洛韦和阿昔洛韦对无细胞VZV蚀斑形成的抑制作用以及阿昔洛韦耐药的VZV对喷昔洛韦的交叉耐药性。第三天测定的喷昔洛韦50%蚀斑减少的表观有效浓度（EC50）显著低于第四天或第五天测定的浓度。在喷昔洛韦存在的情况下蚀斑大小比在阿昔洛韦存在的情况下更小。喷昔洛韦和阿昔洛韦使每个蚀斑中感染细胞数量减少50%的有效浓度分别为1.40和5.00微克/毫升。因此，喷昔洛韦比阿昔洛韦更有效地抑制了正在形成的蚀斑内的感染传播。对通过阿昔洛韦筛选出的5株DNA聚合酶改变的阿昔洛韦耐药VZV毒株进行了喷昔洛韦交叉耐药性检测。它们对阿昔洛韦的耐药性比亲本毒株高11至18倍，但对喷昔洛韦的耐药性仅高4至5倍。携带2'-脱氧核糖3'-羟基的喷昔洛韦三磷酸酯可能比没有3'-羟基的阿昔洛韦三磷酸酯对改变的病毒DNA聚合酶具有更好的亲和力。
