Kukhanova Marina K, Karpenko Inna L, Ivanov Alexander V
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Vavilov St. 32 Moscow, Russia.
Molecules. 2020 Feb 24;25(4):1015. doi: 10.3390/molecules25041015.
This short review is focused on enzymatic properties of human ATP-dependent RNA helicase DDX3 and the development of antiviral and anticancer drugs targeting cellular helicases. DDX3 belongs to the DEAD-box proteins, a large family of RNA helicases that participate in all aspects of cellular processes, such as cell cycle progression, apoptosis, innate immune response, viral replication, and tumorigenesis. DDX3 has a variety of functions in the life cycle of different viruses. DDX3 helicase is required to facilitate both the Rev-mediated export of unspliced/partially spliced human immunodeficiency virus (HIV) RNA from nucleus and Tat-dependent translation of viral genes. DDX3 silencing blocks the replication of HIV, HCV, and some other viruses. On the other hand, DDX displays antiviral effect against Dengue virus and hepatitis B virus through the stimulation of interferon beta production. The role of DDX3 in different types of cancer is rather controversial. DDX3 acts as an oncogene in one type of cancer, but demonstrates tumor suppressor properties in other types. The human DDX3 helicase is now considered as a new attractive target for the development of novel pharmaceutical drugs. The most interesting inhibitors of DDX3 helicase and the mechanisms of their actions as antiviral or anticancer drugs are discussed in this short review.
本简短综述聚焦于人类ATP依赖的RNA解旋酶DDX3的酶学特性以及针对细胞解旋酶的抗病毒和抗癌药物的研发。DDX3属于DEAD盒蛋白家族，这是一个庞大的RNA解旋酶家族，参与细胞过程的各个方面，如细胞周期进程、细胞凋亡、先天免疫反应、病毒复制和肿瘤发生。DDX3在不同病毒的生命周期中具有多种功能。DDX3解旋酶对于促进Rev介导的未剪接/部分剪接的人类免疫缺陷病毒（HIV）RNA从细胞核输出以及病毒基因的Tat依赖性翻译都是必需的。DDX3沉默会阻断HIV、HCV和其他一些病毒的复制。另一方面，DDX通过刺激干扰素β的产生对登革热病毒和乙型肝炎病毒显示出抗病毒作用。DDX3在不同类型癌症中的作用颇具争议。DDX3在一种类型的癌症中作为癌基因起作用，但在其他类型中表现出肿瘤抑制特性。人类DDX3解旋酶现在被认为是新型药物研发的一个新的有吸引力的靶点。本简短综述讨论了最有趣的DDX3解旋酶抑制剂及其作为抗病毒或抗癌药物的作用机制。
