RK-33 Is a Broad-Spectrum Antiviral Agent That Targets DEAD-Box RNA Helicase DDX3X
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 antivi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-01-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/1/170 |
| _version_ | 1797709466800488448 |
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| author | Sundy N. Y. Yang Sarah C. Atkinson Michelle D. Audsley Steven M. Heaton David A. Jans Natalie A. Borg |
| author_facet | Sundy N. Y. Yang Sarah C. Atkinson Michelle D. Audsley Steven M. Heaton David A. Jans Natalie A. Borg |
| author_sort | Sundy N. Y. Yang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T06:36:58Z |
| format | Article |
| id | doaj.art-4f0b210aaf3d40578aff1ed5a75063b4 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T06:36:58Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-4f0b210aaf3d40578aff1ed5a75063b42023-09-03T01:15:02ZengMDPI AGCells2073-44092020-01-019117010.3390/cells9010170cells9010170RK-33 Is a Broad-Spectrum Antiviral Agent That Targets DEAD-Box RNA Helicase DDX3XSundy N. Y. Yang0Sarah C. Atkinson1Michelle D. Audsley2Steven M. Heaton3David A. Jans4Natalie A. Borg5Nuclear Signaling Laboratory, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, AustraliaInfection & Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, AustraliaInfection & Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, AustraliaInfection & Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, AustraliaNuclear Signaling Laboratory, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, AustraliaInfection & Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, AustraliaViral 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.https://www.mdpi.com/2073-4409/9/1/170ddx3xdead-box helicaserk-33viral infectionsmall molecule inhibitor |
| spellingShingle | Sundy N. Y. Yang Sarah C. Atkinson Michelle D. Audsley Steven M. Heaton David A. Jans Natalie A. Borg RK-33 Is a Broad-Spectrum Antiviral Agent That Targets DEAD-Box RNA Helicase DDX3X Cells ddx3x dead-box helicase rk-33 viral infection small molecule inhibitor |
| title | RK-33 Is a Broad-Spectrum Antiviral Agent That Targets DEAD-Box RNA Helicase DDX3X |
| title_full | RK-33 Is a Broad-Spectrum Antiviral Agent That Targets DEAD-Box RNA Helicase DDX3X |
| title_fullStr | RK-33 Is a Broad-Spectrum Antiviral Agent That Targets DEAD-Box RNA Helicase DDX3X |
| title_full_unstemmed | RK-33 Is a Broad-Spectrum Antiviral Agent That Targets DEAD-Box RNA Helicase DDX3X |
| title_short | RK-33 Is a Broad-Spectrum Antiviral Agent That Targets DEAD-Box RNA Helicase DDX3X |
| title_sort | rk 33 is a broad spectrum antiviral agent that targets dead box rna helicase ddx3x |
| topic | ddx3x dead-box helicase rk-33 viral infection small molecule inhibitor |
| url | https://www.mdpi.com/2073-4409/9/1/170 |
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