Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.antiviral.2015.03.010
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dc.titleAntiviral activities of 15 dengue NS2B-NS3 protease inhibitors using a human cell-based viral quantification assay
dc.contributor.authorChu, JJH
dc.contributor.authorLee, RCH
dc.contributor.authorAng, MJY
dc.contributor.authorWang, WL
dc.contributor.authorLim, HA
dc.contributor.authorWee, JLK
dc.contributor.authorJoy, J
dc.contributor.authorHill, J
dc.contributor.authorBrian Chia, CS
dc.date.accessioned2020-08-20T11:43:58Z
dc.date.available2020-08-20T11:43:58Z
dc.date.issued2015-06-01
dc.identifier.citationChu, 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
dc.identifier.issn01663542
dc.identifier.issn18729096
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/173177
dc.description.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.
dc.publisherElsevier BV
dc.sourceElements
dc.subjectAntiviral
dc.subjectDengue
dc.subjectNS2B-NS3
dc.subjectProtease inhibitor
dc.subjectAnthraquinones
dc.subjectAntiviral Agents
dc.subjectCell Line, Tumor
dc.subjectCell Survival
dc.subjectDengue Virus
dc.subjectHepatocytes
dc.subjectHumans
dc.subjectMicrobial Sensitivity Tests
dc.subjectProtease Inhibitors
dc.subjectRNA Helicases
dc.subjectSerine Endopeptidases
dc.subjectViral Load
dc.subjectViral Nonstructural Proteins
dc.typeArticle
dc.date.updated2020-06-23T08:31:35Z
dc.contributor.departmentDEPT OF BIOLOGICAL SCIENCES
dc.contributor.departmentDEPT OF MEDICINE
dc.contributor.departmentMICROBIOLOGY AND IMMUNOLOGY
dc.description.doi10.1016/j.antiviral.2015.03.010
dc.description.sourcetitleAntiviral Research
dc.description.volume118
dc.description.issue118
dc.description.page68-74
dc.description.placeNETHERLANDS
dc.published.statePublished
dc.description.redepositCompleted
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