Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.antiviral.2015.03.010
Title: Antiviral activities of 15 dengue NS2B-NS3 protease inhibitors using a human cell-based viral quantification assay
Authors: Chu, JJH 
Lee, RCH 
Ang, MJY
Wang, WL
Lim, HA
Wee, JLK
Joy, J
Hill, J 
Brian Chia, CS
Keywords: Antiviral
Dengue
NS2B-NS3
Protease inhibitor
Anthraquinones
Antiviral Agents
Cell Line, Tumor
Cell Survival
Dengue Virus
Hepatocytes
Humans
Microbial Sensitivity Tests
Protease Inhibitors
RNA Helicases
Serine Endopeptidases
Viral Load
Viral Nonstructural Proteins
Issue Date: 1-Jun-2015
Publisher: Elsevier BV
Citation: Chu, JJH, Lee, RCH, Ang, MJY, Wang, WL, Lim, HA, Wee, JLK, Joy, J, Hill, J, Brian Chia, CS (2015-06-01). Antiviral activities of 15 dengue NS2B-NS3 protease inhibitors using a human cell-based viral quantification assay. Antiviral Research 118 (118) : 68-74. ScholarBank@NUS Repository. https://doi.org/10.1016/j.antiviral.2015.03.010
Abstract: © 2015 Elsevier B.V. The dengue virus is a mosquito-borne pathogen responsible for an estimated 50-100 million human dengue infections annually. There are currently no approved drugs against this disease, resulting in a major unmet clinical need. The dengue viral NS2B-NS3 protease has been identified as a plausible drug target due to its involvement in viral replication in mammalian host cells. In the past decade, at least 20 dengue NS2B-NS3 protease inhibitors have been reported in the literature with a range of inhibitory activities in protease assays. However, such assays do not shed light on an inhibitor's ability to penetrate human cell membranes where the viral protease resides. In this study, we investigated the antiviral activities of 15 small-molecule and peptide-based NS2B-NS3 inhibitors on dengue serotype 2-infected HuH-7 human hepatocarcinoma cells. Experimental results revealed anthraquinone ARDP0006 (compound 5) to be the most potent inhibitor which reduced dengue viral titer by more than 1 log PFU/mL at 1 μM in our cell-based assays involving HuH-7 and K562 cell lines, suggesting that its scaffold could serve as a lead for further medicinal chemistry studies. Compound 5 was also found to be non-cytotoxic at 1 μM over 3 days incubation on HuH-7 cells using the Alamar Blue cellular toxicity assay.
Source Title: Antiviral Research
URI: https://scholarbank.nus.edu.sg/handle/10635/173177
ISSN: 01663542
18729096
DOI: 10.1016/j.antiviral.2015.03.010
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