Current and potential treatments for ubiquitous but neglected herpesvirus infections.
Current and potential treatments for ubiquitous but neglected herpesvirus infections.
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DOI：
10.1021/cr500255e
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发表时间：
2014-11-26
期刊：
影响因子：
62.1
通讯作者：
Craik, Charles S.
中科院分区：
文献类型：
--
作者：
Gable, Jonathan E.;Acker, Timothy M.;Craik, Charles S.
世界上90%以上的人口感染了疱疹病毒。尽管有这样一个惊人的事实，但只有少数药物被批准用于疱疹病毒感染的一般治疗。迄今为止，所有这些药物都抑制同一种酶，即病毒DNA聚合酶。已经确定了九种人类疱疹病毒，每种病毒都与疾病有关。在免疫能力强的个体中，疱疹病毒感染是令人不快但通常不会危及生命的疾病的原因，如口腔和生殖器疱疹、水痘和带状疱疹、婴儿皮疹（婴儿红疹）和传染性单核细胞增多症（也简称为单核细胞增多症）。在免疫系统不成熟或受损的个体中，疱疹病毒感染可能是毁灭性的。发育障碍、视力和听力丧失、癌症、危及生命的肺炎、脑炎（脑部炎症）和死亡只是疱疹病毒对这部分人群健康造成的部分损失。疱疹病毒生物学的巨大复杂性带来了许多治疗干预的潜在途径，这些途径仍处于起步阶段。然而，在过去的二十年里，疱疹病毒的新疗法取得了进展；这就是本次审查的主题。以前对该主题的评论要么超过10年，要么只涵盖该领域的一个分支。在此，我们提供了疱疹病毒药物发现的全面回顾，重点是该领域的最新进展及其从早期发现到临床开发的进展。重点是小分子抑制剂的开发，因此我们不会详细介绍生物制剂和疫苗的开发。在疫苗开发的背景下，很少有关于抗疱疹生物制剂的工作，这在其他地方进行了审查。然而，我们将讨论一些令人兴奋的靶向病毒多肽的生物制剂，这些生物制剂似乎可以驱动肿瘤的发生，尽管它们不是病毒复制周期所必需的。介绍了必要的疱疹病毒生物学，并可以在其他地方找到更详细的生物学/病毒学综述。通过强调最近在疱疹病毒药物开发方面令人兴奋的工作，以及使其成为可能的历史研究，我们希望激发人们对这种普遍存在但被忽视的病毒家族的许多潜在治疗靶点的兴趣。
More than 90% of the world’s population is infected with a herpesvirus. 1 Despite this staggering fact, only a handful of approved drugs exist for the general treatment of herpesvirus infections. To date, all of these drugs inhibit the same enzyme, the viral DNA polymerase. Nine human herpesviruses have been identified, and each has been associated with disease. In immune-competent individuals, herpesvirus infections are the causes of unpleasant but typically non-life-threatening diseases such as oral and genital herpes, chickenpox and shingles, skin rash in infants (roseola infantum), and infectious mononucleosis (also known simply as mono). In individuals with immature or compromised immune systems, herpesvirus infection can be devastating. Developmental disabilities, loss of sight and hearing, cancer, life-threatening pneumonia, encephalitis (inflammation of the brain), and death comprise only a partial list of the cost herpesviruses have on well being in this subset of the population.The tremendous complexity of herpesvirus biology brings with it many potential avenues for therapeutic interventions that remain in their infancy. However, the past two decades have seen progress toward novel treatments for herpesviruses; this is the subject of the current review. Previous reviews of the subject are either more than 10 years old or cover a subsection of the field. Herein we provide a comprehensive review of herpesvirus drug discovery with an emphasis on the most recent advances in the field and their progression from early discovery to clinical development. The focus is on smallmolecule inhibitor development so we do not cover biologics and vaccine development in as much detail. There is little work on antiherpes biologics outside the context of vaccine development, which is reviewed elsewhere. 2 We will, however, discuss some exciting biologics targeting viral polypeptides that appear to drive oncogenesis, though they are not required for the viral replication cycle. The necessary herpesvirus biology is introduced, and a more detailed review of that biology/virology can be found elsewhere. 3 By highlighting the exciting recent work in herpesvirus drug development, and the historical studies that enabled it, we hope to spur interest in the many potential therapeutic targets for this ubiquitous but neglected virus family.
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影响因子：
4.9
作者：
ABELE, G;ERIKSSON, B;WAHREN, B
通讯作者：
WAHREN, B
影响因子：
2.7
作者：
Bloom, JD;Dushin, RG;DiGrandi, MJ
通讯作者：
DiGrandi, MJ
影响因子：
64.8
作者：
BAYLISS, GJ;WOLF, H
通讯作者：
WOLF, H
影响因子：
5.4
作者：
Bonneau, AM;Kibler, P;Cordingley, MG
通讯作者：
Cordingley, MG
DOI：
10.1073/pnas.78.11.7162
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
BAYLISS, GJ;WOLF, H
通讯作者：
WOLF, H