UNIQUE SPECTRUM OF ACTIVITY OF 9-[(1,3-DIHYDROXY-2-PROPOXY)METHYL]-GUANINE AGAINST HERPESVIRUSES INVITRO AND ITS MODE OF ACTION AGAINST HERPES-SIMPLEX VIRUS TYPE-1
UNIQUE SPECTRUM OF ACTIVITY OF 9-[(1,3-DIHYDROXY-2-PROPOXY)METHYL]-GUANINE AGAINST HERPESVIRUSES INVITRO AND ITS MODE OF ACTION AGAINST HERPES-SIMPLEX VIRUS TYPE-1
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DOI：
10.1073/pnas.80.9.2767
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发表时间：
1983-01-01
期刊：
影响因子：
--
通讯作者：
GRILL, SP
中科院分区：
文献类型：
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作者：
CHENG, YC;HUANG, ES;GRILL, SP
发现鸟苷类似物9-[（1-3-二羟基-2-丙氧基）甲基]鸟嘌呤（DHPG）在不抑制培养物中人宫颈癌细胞生长的浓度下抑制1型单纯疱疹病毒（HSV-1）、2型单纯疱疹病毒、巨细胞病毒和EB病毒复制> 50%。该药物对所有这些病毒的效力大于9-[（2-羟基乙氧基）甲基]鸟嘌呤（阿昔洛韦）。DHPG在病毒复制的早期阶段对HSV-1生长有活性，并且在感染后的较晚时间加入时没有活性。其抗病毒活性是不可逆的。胸苷部分中和了它的作用。DHPG的抗HSV-1活性依赖于病毒诱导的胸苷激酶的诱导和性质。诱导改变病毒胸苷激酶并对阿昔洛韦产生耐药性的病毒变体对DHPG仍然像亲本病毒一样敏感。DHPG对5种不同的HSV变体具有活性，其具有诱导的改变的DNA聚合酶和对阿昔洛韦的抗性。
A guanosine analog, 9-[(1-3-dihydroxy-2-propoxy)methyl]guanine (DHPG), was found to inhibit herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2, cytomegalovirus and Epstein-Barr virus replication by > 50% at concentrations that do not inhibit human cervical carcinoma cell growth in culture. The potency of the drug against all of these viruses is greater than that of 9-[(2-hydroxyethoxy)methyl]guanine (acyclovir). DHPG was active against HSV-1 growth during the early phase of virus replication and had no activity when added at a later time after infection. Its antiviral activity was irreversible. Thymidine partially neutralized its action. The anti-HSV-1 activity of DHPG was dependent on the induction and the properties of virus-induced thymidine kinase. Virus variants that induced altered virus thymidine kinase and became resistant to acyclovir were still as sensitive to DHPG as the parental virus. DHPG is active against 5 different HSV variants with induced altered DNA polymerase and resistance to acyclovir.