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Open AccessArticle

RK-33 Is a Broad-Spectrum Antiviral Agent That Targets DEAD-Box RNA Helicase DDX3X

1
Nuclear Signaling Laboratory, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
2
Infection & Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Current address: Chronic Infectious and Inflammatory Diseases Research, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia.
§
Senior author.
Cells 2020, 9(1), 170; https://doi.org/10.3390/cells9010170
Received: 3 December 2019 / Revised: 18 December 2019 / Accepted: 3 January 2020 / Published: 9 January 2020
Viral disease is one of the greatest burdens for human health worldwide, with an urgent need for efficacious antiviral strategies. While antiviral drugs are available, in many cases, they are prone to the development of drug resistance. A way to overcome drug resistance associated with common antiviral therapies is to develop antivirals targeting host cellular co-factors critical to viral replication, such as DEAD-box helicase 3 X-linked (DDX3X), which plays key roles in RNA metabolism and the antiviral response. Here, we use biochemical/biophysical approaches and infectious assays to show for the first time that the small molecule RK-33 has broad-spectrum antiviral action by inhibiting the enzymatic activities of DDX3X. Importantly, we show that RK-33 is efficacious at low micromolar concentrations in limiting infection by human parainfluenza virus type 3 (hPIV-3), respiratory syncytial virus (RSV), dengue virus (DENV), Zika virus (ZIKV) or West Nile virus (WNV)—for all of which, no Food and Drug Administration (FDA)-approved therapeutic is widely available. These findings establish for the first time that RK-33 is a broad-spectrum antiviral agent that blocks DDX3X’s catalytic activities in vitro and limits viral replication in cells. View Full-Text
Keywords: DDX3X; DEAD-box helicase; RK-33; viral infection; small molecule inhibitor DDX3X; DEAD-box helicase; RK-33; viral infection; small molecule inhibitor
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Yang, S.N.Y.; Atkinson, S.C.; Audsley, M.D.; Heaton, S.M.; Jans, D.A.; Borg, N.A. RK-33 Is a Broad-Spectrum Antiviral Agent That Targets DEAD-Box RNA Helicase DDX3X. Cells 2020, 9, 170.

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