Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 11, Issue 5, Pages 956-962Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.9b00681
Keywords
DDX3X; host factors; DENV; antiviral agents; resistance; immunofluorescence
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Funding
- First Health Pharmaceuticals B.V.
- Tuscany Region [DD3242/2009]
- CNR
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In the absence of effective drugs or vaccines for the treatment of the five Dengue Virus serotypes, the search for novel antiviral drugs is of primary importance for the scientific community. In this context, drug repurposing represents the most used strategy; however, the study of host targets is now attracting attention since it allows identification of broad-spectrum drugs endowed with high genetic barrier. In the last ten years our research group identified several small molecules DDX3X inhibitors and proved their efficacy against different viruses including novel emerging ones. Herein, starting from a screening of our compounds, we designed and synthesized novel derivatives with potent activity and high selectivity. Finally, we synthesized a fluorescent inhibitor that allowed us to study DDX3X cellular localization during DENV infection in vitro. Immunofluorescence analysis showed that our inhibitor colocalized with DDX3X, promoting the reduction of infected cells and recovering the number of viable cells.
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