Muller Clotilde, Alain Sophie, Baumert Thomas F, Ligat Gaëtan, Hantz Sébastien
INSERM, CHU Limoges, University of Limoges, RESINFIT, U1092, 87000 Limoges, France.
CHU Limoges, Laboratoire de Bactériologie-Virologie-Hygiène, National Reference Center for Herpesviruses (NRCHV), 87000 Limoges, France.
Life (Basel). 2021 Feb 16;11(2):150. doi: 10.3390/life11020150.
Herpesviruses are the causative agents of several diseases. Infections are generally mild or asymptomatic in immunocompetent individuals. In contrast, herpesvirus infections continue to contribute to significant morbidity and mortality in immunocompromised patients. Few drugs are available for the treatment of human herpesvirus infections, mainly targeting the viral DNA polymerase. Moreover, no successful therapeutic options are available for the Epstein-Barr virus or human herpesvirus 8. Most licensed drugs share the same mechanism of action of targeting the viral polymerase and thus blocking DNA polymerization. Resistances to antiviral drugs have been observed for human cytomegalovirus, herpes simplex virus and varicella-zoster virus. A new terminase inhibitor, letermovir, recently proved effective against human cytomegalovirus. However, the letermovir has no significant activity against other herpesviruses. New antivirals targeting other replication steps, such as capsid maturation or DNA packaging, and inducing fewer adverse effects are therefore needed. Targeting capsid assembly or DNA packaging provides additional options for the development of new drugs. In this review, we summarize recent findings on capsid assembly and DNA packaging. We also described what is known about the structure and function of capsid and terminase proteins to identify novels targets for the development of new therapeutic options.
疱疹病毒是多种疾病的病原体。在免疫功能正常的个体中，感染通常较轻或无症状。相比之下，疱疹病毒感染在免疫功能低下的患者中仍然导致显著的发病率和死亡率。用于治疗人类疱疹病毒感染的药物很少，主要针对病毒DNA聚合酶。此外，对于爱泼斯坦-巴尔病毒或人类疱疹病毒8没有成功的治疗选择。大多数已获许可的药物具有相同的作用机制，即靶向病毒聚合酶从而阻断DNA聚合。人类巨细胞病毒、单纯疱疹病毒和水痘-带状疱疹病毒对抗病毒药物的耐药性已被观察到。一种新的末端酶抑制剂来特莫韦最近被证明对人类巨细胞病毒有效。然而，来特莫韦对其他疱疹病毒没有显著活性。因此，需要针对其他复制步骤（如衣壳成熟或DNA包装）且产生较少不良反应的新型抗病毒药物。靶向衣壳组装或DNA包装为新药开发提供了额外的选择。在这篇综述中，我们总结了衣壳组装和DNA包装的最新研究结果。我们还描述了关于衣壳和末端酶蛋白的结构和功能的已知信息，以确定新治疗选择开发的新靶点。
