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Small Molecule Inhibitor Discovery for Dengue Virus Protease Using High-Throughput Screening

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Dengue

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1138))

Abstract

Dengue virus (DENV), a member of mosquito-borne flavivirus genus in the Flaviviridae family, is an important human pathogen of global significance. DENV infections are the most common arbovirus infections in the world, causing more than ~300 million cases annually. Although majority of infections result in simple self-limiting disease known as dengue fever which resolve in 7–10 days, ~500,000 cases lead to more severe complications known as dengue hemorrhagic fever/dengue shock syndrome, more frequently observed in secondary infections due to an antibody-dependent enhancement mechanism, resulting in ~25,000 deaths. Currently, there are no vaccines or antiviral drug available for the treatment of DENV infections. Several viral and host proteins have been identified as potential targets for drug development. Some of the viral targets have enzyme activities that play essential roles in viral RNA replication for which in vitro high-throughput screening (HTS) assays have been developed. In this chapter, we describe an in vitro assay for the viral serine protease that has been successfully adapted to HTS format and has been used to screen several thousand compounds to identify inhibitors of the viral protease.

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Acknowledgments

The research was supported by NIH grants AI082068 and AI70791 to R. P., U54 AI057159 to NSRB, and the Cosmos Club Foundation Young Scholars Award to M.M.

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Authors and Affiliations

  1. Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    Mark Manzano

  2. Prime Time Life Sciences, LLC, Germantown, MD, USA

    Janak Padia

  3. Department of Microbiology & Immunology, Georgetown University, Washington, DC, USA

    Radhakrishnan Padmanabhan

Authors
  1. Mark Manzano
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  2. Janak Padia
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  3. Radhakrishnan Padmanabhan
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Corresponding author

Correspondence to Radhakrishnan Padmanabhan .

Editor information

Editors and Affiliations

  1. Georgetown University Medical Center Dept. of Microbiology and Immunology, Washington, District of Columbia, USA

    Radhakrishnan Padmanabhan

  2. Duke-NUS GMS Singapore Emerging Infectious Diseases, Singapore, Singapore

    Subhash G. Vasudevan

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Manzano, M., Padia, J., Padmanabhan, R. (2014). Small Molecule Inhibitor Discovery for Dengue Virus Protease Using High-Throughput Screening. In: Padmanabhan, R., Vasudevan, S. (eds) Dengue. Methods in Molecular Biology, vol 1138. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0348-1_20

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  • DOI: https://doi.org/10.1007/978-1-4939-0348-1_20

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-0347-4

  • Online ISBN: 978-1-4939-0348-1

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