Field A K, Tuomari A V, McGeever-Rubin B, Terry B J, Mazina K E, Haffey M L, Hagen M E, Clark J M, Braitman A, Slusarchyk W A
Squibb Institute for Medical Research, Princeton, NJ 08543-4000.
Antiviral Res. 1990 Jan;13(1):41-52. doi: 10.1016/0166-3542(90)90043-7.
(+-)-(1 alpha,2 beta,3 alpha)-9-[2,3-bis(hydroxymethyl)cyclobutyl] guanine [(+-)-BHCG or SQ 33,054] is a newly synthesized nucleoside analog with potent and selective antiviral activity against members of the herpesvirus group, including human cytomegalovirus. The activity against a thymidine kinase deficient HSV-2 mutant was 25-fold poorer than against the parent virus, suggesting that phosphorylation is an important prerequisite for antiviral activity against HSV-2. (+-)-BHCG is readily phosphorylated by purified HSV-1 thymidine kinase, and BHCG triphosphate synthesized enzymatically is a selective inhibitor of HSV-1 DNA polymerase. (+-)-BHCG did not inhibit host cell growth at concentrations at least 1000-fold higher than HSV-2 inhibitory concentrations. Subcutaneous administration of (+-)-BHCG was protective against HSV-1 systemic infections in mice. BHCG is an exciting antiviral agent and represents a new class of nucleoside analogs.
（±）-（1α，2β，3α）-9-[2,3-双（羟甲基）环丁基]鸟嘌呤[（±）-BHCG或SQ 33,054]是一种新合成的核苷类似物，对疱疹病毒组的成员，包括人巨细胞病毒，具有强效和选择性抗病毒活性。对胸苷激酶缺陷的HSV-2突变体的活性比对亲本病毒的活性低25倍，这表明磷酸化是抗HSV-2抗病毒活性的重要前提。（±）-BHCG很容易被纯化的HSV-1胸苷激酶磷酸化，酶促合成的BHCG三磷酸是HSV-1 DNA聚合酶的选择性抑制剂。在浓度至少比HSV-2抑制浓度高1000倍时，（±）-BHCG不抑制宿主细胞生长。皮下注射（±）-BHCG对小鼠的HSV-1全身感染具有保护作用。BHCG是一种令人兴奋的抗病毒药物，代表了一类新的核苷类似物。
