De Clercq E, Bernaerts R
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
J Biol Chem. 1987 Nov 5;262(31):14905-11.
5-Ethyl-2'-deoxyuridine (EDU) is a potent and selective inhibitor of the replication of herpes simplex virus type 1 (HSV-1) and 2 (HSV-2), which is currently being pursued for the topical treatment of HSV-1 and HSV-2 infections in humans. Using [4-14C]EDU as the radiolabeled analogue of EDU, it was ascertained that, at antivirally active doses, EDU is phosphorylated to a much greater extent by HSV-infected Vero cells than by mock-infected cells. Within the HSV-1-infected cells, EDU was incorporated to a much greater extent into viral DNA than cellular DNA. Using varying doses of EDU, a close correlation was found between the incorporation of EDU into viral DNA, the inhibition of viral DNA synthesis, and the inhibition of virus yield. It is postulated that the selectivity of EDU as an antiviral agent depends on both its preferential phosphorylation by the virus-infected cell and its preferential incorporation into viral DNA. The latter than results in a suppression of viral DNA synthesis and, hence, shutoff of viral progeny formation.
5-乙基-2'-脱氧尿苷（EDU）是一种强效且具有选择性的单纯疱疹病毒1型（HSV-1）和2型（HSV-2）复制抑制剂，目前正被用于人类HSV-1和HSV-2感染的局部治疗。使用[4-¹⁴C]EDU作为EDU的放射性标记类似物，已确定在抗病毒活性剂量下，被HSV感染的Vero细胞对EDU的磷酸化程度远高于 mock感染的细胞。在被HSV-1感染的细胞内，EDU掺入病毒DNA的程度远高于细胞DNA。使用不同剂量的EDU，发现EDU掺入病毒DNA、抑制病毒DNA合成以及抑制病毒产量之间存在密切相关性。据推测，EDU作为抗病毒剂的选择性取决于其被病毒感染细胞优先磷酸化以及优先掺入病毒DNA。后者进而导致病毒DNA合成受到抑制，从而阻断病毒子代的形成。
