AAC：酶类抑制剂或可有效抑制单纯疱疹病毒的复制

  发表在国际杂志Antimicrobial Agents and Chemotherapy上的一篇研究论文中，来自圣路易斯大学的研究人员报道了一组转核甙酸酶超家族（NTS）酶类分子，其可以作为潜在的抑制剂来治疗单纯疱疹病毒感染。

  研究者Morrison说道，阿昔洛韦可以有效抑制单纯疱疹病毒，但相比阿昔洛韦而言，NTS抑制剂可以通过一种不同的机制来有效抑制病毒，其或可以同当前药物结合来完全有效地清除病毒。单纯疱疹病毒（HSV）性脑炎被认为是HSV通过神经直接传播感染而致病，研究人员指出，超过一半的美国人都受到唇疱疹（HSV-1）的影响，且20%的个体都遭受过生殖器疱疹（HSV-2）的影响。

  文章中，研究者调查了是否NTS酶类抑制剂可以抑制HSV-1和HSV-2的感染，这种抑制剂可以抑制病毒基因组的积累以及感染性颗粒的集聚，同时还可以在病毒DNA复制期间阻断病毒的复制循环，六分之五的NTS抑制剂都可以阻断另外一种疱疹病毒-巨细胞病毒的复制。

  目前研究人员主要研究来鉴别出每一种抑制剂抑制病毒复制的具体机制，而其中有一种化合物可以有效抑制动物模型的感染，后期研究者将继续研究病毒的进化及其同抑制剂的作用方式；当前治疗疱疹病毒感染的疗法主要依赖于病毒DNA聚合酶的核苷类似物抑制剂，目前有一些新型制剂仍在临床开发中，其尚不能有效抑制疱疹病毒的感染。（转化医学网360zhyx.com）

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Inhibitors of Nucleotidyltransferase Superfamily Enzymes Suppress Herpes Simplex Virus Replication
Antimicrob. Agents Chemother doi: 10.1128/AAC.03875-14
John E. Tavis, Hong Wang, Ann E. Tollefson, Baoling Ying, Maria Korom, Xiaohong Cheng, Feng Cao*, Katie L. Davis, William S. M. Wold and Lynda A. Morrison
Herpesviruses are large double-stranded DNA viruses that cause serious human diseases. Herpesvirus DNA replication depends on multiple processes typically catalyzed by nucleotidyltransferase superfamily (NTS) enzymes. Therefore, we investigated whether inhibitors of NTS enzymes would suppress replication of herpes simplex virus 1 (HSV-1) and HSV-2. Eight of 42 NTS inhibitors suppressed HSV-1 and/or HSV-2 replication by >10-fold at 5 μM, with suppression at 50 μM reaching ∼1 million-fold. Five compounds in two chemical families inhibited HSV replication in Vero and human foreskin fibroblast cells as well as the approved drug acyclovir did. The compounds had 50% effective concentration values as low as 0.22 μM with negligible cytotoxicity in the assays employed. The inhibitors suppressed accumulation of viral genomes and infectious particles and blocked events in the viral replication cycle before and during viral DNA replication. Acyclovir-resistant mutants of HSV-1 and HSV-2 remained highly sensitive to the NTS inhibitors. Five of six NTS inhibitors of the HSVs also blocked replication of another herpesvirus pathogen, human cytomegalovirus. Therefore, NTS enzyme inhibitors are promising candidates for new herpesvirus treatments that may have broad efficacy against members of the herpesvirus family.