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Review
. 2020 Feb 24;25(4):1015.
doi: 10.3390/molecules25041015.

DEAD-box RNA Helicase DDX3: Functional Properties and Development of DDX3 Inhibitors as Antiviral and Anticancer Drugs

Marina K Kukhanova  1 , Inna L Karpenko  1 , Alexander V Ivanov  1
Affiliations
Review

DEAD-box RNA Helicase DDX3: Functional Properties and Development of DDX3 Inhibitors as Antiviral and Anticancer Drugs

Marina K Kukhanova et al. Molecules. .

Abstract

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.

Keywords: DEAD-box family RNA helicases; anticancer drug; antiviral drug; inhibitors; physico-chemical properties; virus life cycle.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(a) Domain structure of the DDX3 helicase. (b) Motifs of RecA-like domains supporting ATPase and helicase activities.
Figure 2
Figure 2
Local strand separation by DDX3 helicase trimer.
Figure 3
Figure 3
Hypothetical mechanism of involvement of the DDX3 helicase in the export of unspliced/partially spliced HIV RNA from nucleus to cytoplasm. CRM1—cellular export shuttle protein; Rev—shuttle protein with nuclear localization signal and a nuclear export signal. RANGTP—GTPase, Tat—HIV translation factor.
Figure 4
Figure 4
DDX3 inhibitors with anticancer activity.
See this image and copyright information in PMC

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