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天然产物抗疱疹病毒感染的生物活性。

Bioactive activities of natural products against herpesvirus infection.

机构信息

College of Pharmacy, Research Institute of Pharmaceutical Sciences, and Institute for Microorganisms, Kyungpook National University, Daegu, 702-701, Republic of Korea.

出版信息

J Microbiol. 2013 Oct;51(5):545-51. doi: 10.1007/s12275-013-3450-9. Epub 2013 Oct 31.

Abstract

More than 90% of adults have been infected with at least one human herpesvirus, which establish long-term latent infection for the life of the host. While anti-viral drugs exist that limit herpesvirus replication, many of these are ineffective against latent infection. Moreover, drug-resistant strains of herpesvirus emerge following chemotherapeutic treatment. For example, resistance to acyclovir and related nucleoside analogues can occur when mutations arise in either HSV thymidine kinase or DNA polymerases. Thus, there exists an unmet medical need to develop new anti-herpesvirus agents with different mechanisms of action. In this Review, we discuss the promise of anti-herpetic substances derived from natural products including extracts and pure compounds from potential herbal medicines. One example is Glycyrrhizic acid isolated from licorice that shows promising antiviral activity towards human gammaherpesviruses. Secondly, we discuss anti-herpetic mechanisms utilized by several natural products in molecular level. While nucleoside analogues inhibit replicating herpesviruses in lytic replication, some natural products can disrupt the herpesvirus latent infection in the host cell. In addition, natural products can stimulate immune responses against herpesviral infection. These findings suggest that natural products could be one of the best choices for development of new treatments for latent herpesvirus infection, and may provide synergistic anti-viral activity when supplemented with nucleoside analogues. Therefore, it is important to identify which natural products are more efficacious anti-herpetic agents, and to understand the molecular mechanism in detail for further advance in the anti-viral therapies.

摘要

超过 90%的成年人至少感染过一种人类疱疹病毒,这些病毒会在宿主的一生中建立长期潜伏感染。虽然存在限制疱疹病毒复制的抗病毒药物,但其中许多药物对潜伏感染无效。此外,在化学治疗后,疱疹病毒会出现耐药株。例如,当 HSV 胸苷激酶或 DNA 聚合酶发生突变时,就会出现对阿昔洛韦和相关核苷类似物的耐药性。因此,开发具有不同作用机制的新型抗疱疹病毒药物存在未满足的医疗需求。在这篇综述中,我们讨论了从天然产物中获得的抗疱疹物质的前景,包括来自潜在草药的提取物和纯化合物。一个例子是从甘草中分离出的甘草酸,它对人类γ疱疹病毒表现出有希望的抗病毒活性。其次,我们讨论了几种天然产物在分子水平上利用的抗疱疹机制。虽然核苷类似物可以抑制溶细胞复制中的复制疱疹病毒,但一些天然产物可以破坏宿主细胞中的疱疹病毒潜伏感染。此外,天然产物可以刺激针对疱疹病毒感染的免疫反应。这些发现表明,天然产物可能是开发潜伏疱疹病毒感染新治疗方法的最佳选择之一,并且当与核苷类似物联合使用时,可能提供协同抗病毒活性。因此,确定哪些天然产物是更有效的抗疱疹药物,并详细了解其分子机制,对于推进抗病毒疗法非常重要。

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