Wathen Michael W
Infectious Diseases Research, Pharmacia Corp, Kalamazoo, MI 49001, USA.
Rev Med Virol. 2002 May-Jun;12(3):167-78. doi: 10.1002/rmv.354.
While the treatment of herpes simplex virus with acyclovir and similar nucleoside analogues was one of the first success stories in antiviral chemotherapy, substantial unmet medical needs remain for herpesvirus diseases. In particular, the increasing numbers of immunosuppressed people due to AIDS, transplantation, cancer and aging has driven the need for improved antivirals to treat diseases caused by human cytomegalovirus (HCMV). Currently available drugs for the treatment of HCMV diseases are less than ideal agents due to issues of toxicity, modest efficacy and poor oral bioavailability. High throughput screening of large compound collections for inhibitors of specific viral enzymes or inhibition of viral growth in cell culture have identified a number of new HCMV inhibitors at several pharmaceutical companies. These compounds act by inhibition of novel molecular targets such as the viral protein kinase, viral protease and viral proteins involved in DNA cleavage/packaging. In addition, novel non-nucleoside inhibitors of the herpesvirus DNA polymerase have recently been described. This review will summarise some of these research efforts and will focus on non-nucleoside compounds that directly inhibit a viral process.
虽然用阿昔洛韦和类似核苷类似物治疗单纯疱疹病毒是抗病毒化疗首批成功案例之一，但疱疹病毒疾病仍存在大量未满足的医疗需求。特别是，由于艾滋病、移植、癌症和老龄化导致免疫抑制人群数量不断增加，促使人们需要改进抗病毒药物来治疗由人类巨细胞病毒（HCMV）引起的疾病。目前用于治疗HCMV疾病的药物由于毒性、疗效一般和口服生物利用度差等问题，并非理想药物。几家制药公司通过对大量化合物库进行高通量筛选以寻找特定病毒酶的抑制剂或抑制细胞培养中病毒生长，已鉴定出多种新型HCMV抑制剂。这些化合物通过抑制新型分子靶点发挥作用，如病毒蛋白激酶、病毒蛋白酶以及参与DNA切割/包装的病毒蛋白。此外，最近还报道了疱疹病毒DNA聚合酶的新型非核苷抑制剂。本综述将总结其中一些研究工作，并将重点关注直接抑制病毒过程的非核苷化合物。
