Abstract
BackgroundDengue infection is an endemic infectious disease and it can lead to dengue fever, dengue hemorrhagic fever, and/or dengue shock syndromes. Dengue NS2B/NS3 protease complex is essential for viral replication and is a primary target for anti-dengue drug development. In this study, a NS2B/NS3 protease inhibition assay was developed using AlphaScreen® beads and was used to screen compounds for their protease inhibition activities. MethodsThe assay system utilized a known NS2B/NS3 peptide substrate, a recombinant of NS2B/NS3 protease with proprietary StrepTactin® donor and nickel chelate acceptor beads in 384-well format. ResultsThe optimized assay to screen for NS2B/NS3 protease inhibitors was demonstrated to be potentially useful with reasonable zʹ factor, coefficient variance and signal to background ratio. However, screening of synthesized thioguanine derivatives using the optimized AlphaScreen® assay revealed weak NS2B/NS3 inhibition activities. ConclusionThe AlphaScreen® assay to screen for NS2B/NS3 protease inhibitors is potentially applicable for high throughput screening.
Highlights
Dengue infection is an endemic infectious disease found mainly in tropical and subtropical regions
The AlphaScreenÒ assay to screen for NS2B/NS3 protease inhibitors is potentially applicable for high throughput screening
We have developed a NS2B/NS3 protease inhibition assay using AlphaScreenÒ beads and followed by screening of the synthesized thioguanine derivatives for their possible anti-dengue activities
Summary
Dengue infection is an endemic infectious disease found mainly in tropical and subtropical regions. According to the World Health Organization (WHO), nearly 50e100 million dengue infection cases occur every year. Secondary infection with a heterologous serotype is a risk factor for developing dengue hemorrhagic fever or dengue shock syndrome [4]. Dengue infection is an endemic infectious disease and it can lead to dengue fever, dengue hemorrhagic fever, and/or dengue shock syndromes. Dengue NS2B/NS3 protease complex is essential for viral replication and is a primary target for anti-dengue drug development. A NS2B/NS3 protease inhibition assay was developed using AlphaScreenÒ beads and was used to screen compounds for their protease inhibition activities.
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